Pharmaceutical - Quality - Control Chap 1 10

QUANTITATIVE PHARMACEUTICAL CHEMISTRY
Introduction
o Precipitates in products
(Topic 1: Definition)
Quantitative Pharmaceutical Topic 3: quality and
Chemistry
➢ Application of the procedures of (Quality control)
quantitative analytical chemistry
➢ The analysis and determination of the purity Quality
of drugs and chemicals used in pharmacy,
especially those official in The United States ➢ Defined as the sum of all factors which
contribute directly or indirectly to the safety,
Pharmacopeia and The National Formulary
effectiveness, and reliability of the product.
➢ Analysis of the chemical constituents found
in the human body whose altered Quality Control
concentrations during disease states serve
as diagnostic aids in the practice of ➢ These properties are built into drug products
medicine. through research and during the
➢ Analysis of medicinal agents and their manufacturing process by procedures.
metabolites found in biological systems. ➢ Quality control guarantees within
reasonable limits that a drug product
Topic 2: modern practice o Free of impurities
o Physically and chemically stable
o Contains an amount of active
(Of pharmacy) ingredient(s) as stated on the label
o Provides optimal release of active
➢ Must have a working knowledge if they are ingredient(s) when the product is
to advice medical practitioners on drug
administered
quality
o Alert health professionals to the
influence which drugs may have on Topic 4: methods of
clinical laboratory methods
o Monitor drug levels during therapy (analysis)
➢ Pharmacists is responsible for initiating steps
to determine if indeed the product is Volumetric Analysis
defective
➢ Determination of the volume of a solution of
o Calling and advising the drug
known concentration required to react with
manufacturer of the problem
a given amount of the substance to be
involving the product
analyzed.
o Analyzing the preparation in the
➢ 3 techniques depending on the nature of
prescription laboratory
reactions:
▪ Borrowing needed o Aced-Base Titration – involve the
equipment from a clinical
reaction of an acid and a base.
laboratory if necessary
o Redox Titration – reaction between
o Sending a portion of the sample to a analyte and titrant as the key
private laboratory for analysis
reaction.
o A combination of all these steps.
o Complexometric Titration – involves
➢ Pharmacists who have reason to believe
the formation of a colored complex
that a drug product is not of proper quality
compound.
and appears to be defective, because:
➢ Essential terms for Volumetric Analysis
o Improper labeling
o Molarity – the number of gram moles
o Discoloration of a solute dissolved per liter of
o Presence of cloudiness solution
o Crystals
NORIENE MAIQUEZ 1
▪ It must be checked against

presence of any air bubble
within the liquid.
▪ Read the lower meniscus for
clear liquids/solutions
▪ Read the upper meniscus for
dark colored
solutions/liquids.
o Molality – the number of moles of
the substance dissolved in 1kg of
the solvent
o Normality – the number of gram

equivalents of the substance Burette
dissolved per liter of the solution.
o Pipette – used to draw a definite

o Titration – the procedure of volume of liquids and transfer it to
ascertaining the volume of one the conical flask/beaker etc.
solution essential to react entirely ▪ Liquid should be allowed to
with a definite volume of another drain out from the pipette on
solution of known concentration its own and some portion
o Titrant – the solution of known remains inside it which
concentration (strength). should be drained out by
o Titrate – the solution whose touching the tip of the
concentration (strength) to be pipette to the mouth of the
ascertained. conical flask/beaker.
o Indicator – the reagent which
specifies the endpoint or equivalent
point of the titration Volumetric
➢ Apparatus and Essential Reagents
o Performed with solutions made with
Pipette
distilled or deionized water
o Requires highly accurate graduated
apparatus like burette, pipette,
graduated flasks etc. which should
be rinsed properly with distilled or
deionized water.
▪ Must not contain any o Graduated Flask (Volumetric Flask) –
contaminants and must not used to prepare solutions of known
be rinsed with hot water. strength
o Hot solutions should not be used for
measurement with burette or
pipettes.
o Burette – used to deliver accurate
volumes of liquid within its range.
NORIENE MAIQUEZ 2
M – the molar ratio of the analyte versus the

reactant, obtained from the balanced chemical
equation.
Va – the pipetted-out volume of the analyte,

expressed in liters.
Volumetric
Physicochemical Methods
Flask
➢ Analysis are based on some specific
physical or chemical property or properties
of the substance being analyzed.
➢ The measurement of these properties
requires the utilization of an instrumental
technique
o Indicators – used to determine the ➢ Commonly employ instrumental techniques
end point i.e., the completion of as applied in quantitative pharmaceutical
reaction. chemistry are:
▪ Require external indicators o Chromatography – a process for
for detecting the end points separating components of a mixture.
which essentially means the Different components of the mixture
change in pH of the system. travel through the stationary phase
▪ Common examples of at different speeds, causing them to
indicators are: separate from one another.
• Phenolphthalein – for
strong acid vs strong
base rxn
• Methyl orange – for
strong acid vs weak
base rxn
• Starch – for titrations
involving iodine and
thiosulfate
• Potassium chromate
& Fluorescein – for
silver nitrate titrations.
o Many non-acid-base titrations
require the maintenance of a
constant pH throughout the titration o Spectrometry – measurement of the
and in such cases, buffer solutions interactions between light and
may be used for the purpose. matter, and the reactions and
➢ Calculations measurement of radiation intensity
and wavelength.
▪ Method of studying and
measuring a specific
spectrum, and it’s widely
used for the spectroscopic
Where: analysis of sample materials.
o Electrometry
Ca – concentration of analyte, expressed in o Thermal conductimetry
molarity o Refractometry
o Polarimetry
Ct – concentration of titrant, expressed in
molarity Gravimetric Analysis
Vt – the consumed volume of the titrant, ➢ Separation by extraction, precipitation, or
expressed in liters other means of the constituent to be
NORIENE MAIQUEZ 3
determined either in the natural state or in Notes 2:

the form of a definite compound the
composition and the weighing of the ➢ The theoretical consideration applicable in
resulting product. any given analysis are inherently part of the
o An analyte is the substance to be analytical procedure. Should be mastered
analyzed before a determination is made,
o A precipitating reagent is the ➢ Should be carefully applied throughout
reactant used to precipitate the each step of the procedure.
analyte
o One advantage of gravimetric
analysis compared to volumetric
analysis (titrimetric analysis) is that
there is greater likelihood of any
impurities being seen, and therefore
a correction can be applied.
Special Methods
➢ Those which require a distinct type of
technique, such as alkaloidal assaying.
Notes 1:
➢ Official assay methods serve as an exact
measure of the purity of a substance only
when the results are considered in
conjunction with the qualitative tests.
➢ In the assay of zinc oxide, the
determination of the purity of the oxide by
assay must follow qualitative tests for other
metals which is present would be estimated
as zinc oxide.
NORIENE MAIQUEZ 4
Chapter 1
Remarks and General Directions
(Topic 1: cleaning solution)
➢ Good cleaning solution for glassware can

be prepared by dissolving 200g of sodium
dichromate in 100ml of water and add
1500ml of sulfuric acid slowly with stirring.
➢ Solution should be stored in a thick-walled, Rubber
glass-stoppered bottle and used repeatedly Policeman
for cleaning glass and porcelain ware until it
deposits a large amount of solid material or
turns green.
(Topic 4: reagents)
(Topic 2: wash bottles) ➢ Used in quantitative analysis must be pure.
➢ Conform to the requirements of the United
➢ Use in quantitative work usually consist of States Pharmacopeia (USP) and the
rubber-stoppered National Formulary (NF). Should be used in
➢ 500 to 1000ml capacity all assays which have for their purpose the
➢ Necks of wash bottles for use with hot water establishment of the strength or quality of
should be wrapped with asbestos paper or official substances.
twine or other suitable material. ➢ Wide range of chemical reagents of various
➢ To bore a hole through a rubber stopper, grades, depending on purity are available.
dip the end of the borer in a strong solution ➢ The choice of reagents depends mainly on
of sodium hydroxide or in glycerin before the use of which they are intended.
starting to bore.
➢ Generally used in industry and
➢ Wash bottles made of polyethylene are also
Technical Grade not for analytical work
suitable for quantitative analysis. are Commercial ➢ It is not pure enough to be
reagents. offered for food, drug, or
medicinal use of any kind.
➢ Analyzed for the absence of
certain impurities
➢ They are satisfactory for
pharmaceutical analysis and
Wash common laboratory
requirements.
➢ Acceptance for food, drug, or
Bottle NF or USP Grade
medicinal use.
➢ Standards for chemical and
biological drug substances,
dosage forms, compounded
preparations, excipients,
(Topic 3: policeman) medical devices, and dietary
supplements.
➢ Purer than the USP or
CP Grade
➢ A piece of soft rubber tubing fitted to the commercial grades, but its
Chemical
end of a glass rod. purity varies with the source and
(Chemical Pure)
type of substance.
➢ 20cm long
➢ Used in many analytical
➢ 5-7 mm diameter operations, their specifications
Reagent Grade
➢ With plain annealed ends. are those drown up by the ACS
Chemical
➢ American Chemical Society
(ACS). Acceptable for food,
NORIENE MAIQUEZ 5
drug, or medicinal use and can Wash bottles

be used for ACS applications or Crucible
for general procedures that • For drying &
requires stringent quality Cleaning & Desiccators provides drying
specifications and purity of 95% Others atmosphere
➢ Analyze to ensure that they Rubber
contain less the maximum limits policeman
of impurities. Watch glass •
➢ Labeled: “meets ACS
specification, analytical
reagents.” (Topic 7: SAMPLING)
➢ Equal to and often superior to
the ACS substances in quality
Primary ➢ It is recommended that gross sample of
➢ Use in primary standardization
Standard-Grade
➢ Approach 100% purity and are vegetable drugs in which the component
Chemicals
used to standardized solutions at parts are 1cm or less in any dimension, and
a very high degree of accuracy. all powdered or ground drugs, be taken by
means of a sampler which removes a core
from the top to the bottom of the container,
Topic 5: purity and not less than 2 cores being in opposite
directions; and that when the total weight
(Strength requirements) of the drug to be sampled is less than 100kg
(220 lb.) at least 250g shall constitute and
➢ Purity and strength are usually expressed in official sample.
terms of percent. ➢ When the total weight of a drug to be
➢ Official requirements of purity and strength sampled is less than 10kg, it is
pertain only when the official methods of recommended that the above methods be
assay are employed. followed but that somewhat smaller
➢ The requirement that hydrochloric acid quantities be withdrawn, and in no case
contain “not less than 35 percent and not shall the final official sample weigh less than
more than 38 percent of HCl” 125g.
➢ An alternative to withdrawing of official
Topic 6: Materials Required samples according to methods
o The official sample may consist of
(Apparatus & Instrument)

the total amount of a direct
purchase made by officials charged
• Strictly use for with enforcement of a federal, state,
samples and or municipal food and drugs acts.
Analytical
Weight primary standard
Balance
Topic 8: Correct laboratory
Measurement (weight
accurately)
Top Load • Rough weighing
Volumetric • Very accurate (& analytical techniques)
flask
Volumetric • Transfer pipette – ➢ Steps in quantitative analytical
pipette 2nd accurate determination
• Geissler’s (use for 1. PRIMARY CONSIDERATION
Volume
acids) • Total amount of a
Measurement
Burette • Mohr (use for base) Proximate CLASS or GROUP of
• Teflon (use for acid Nature of active constituents
and base) Analysis • Amount of a SINGLE
Graduated • Least accurate Ultimate CHEMICAL SPECIES
cylinder in a sample.
Funnel • Titrimetric
Gooch • Suction flask Classical
• Gravimetric
Crucible Based on • Spectrometric
• Use of vacuum Instrumental
Filtration Nature of • Polarimetric etc.
when substance Methods • Water content
Fritted are colloidal, Miscellaneous • Ash content
gelatinous and • Acid value etc.
very small.
NORIENE MAIQUEZ 6
Topic 9: Calculation of
• Moisture content
Ultra-micro • <1mg
Based on
Micro • 1 to 10mg
(Results And errors)
Sample
Semi-micro • 10 to 100mg
Size
Macro • 100 to 1000mg
2. SAMPLE PREPARATION ➢ Manifest themselves by slight variations in a
Indeterminate
➢ The actual sample is so large that it is impossible series of observations made by the observer
to work with it reasonably under identical conditions.
Errors
➢ The sampling procedure enables the analyst to ➢ Intangible and difficult to detect
obtain a sample convenient in size that fairly e.g. differences in the judgement and skill of
represent the average composition of the bulk analyst.
material.
➢ Recur in a constant manner in each of a
➢ Sampling techniques, however, are seldom series of determinations.
emphasized in elementary analysis. ➢ Possible to partially determine their value
3. ISOLATION OF THE ANALYTE and reduce their effect on the final result.
➢ After sampling, the sample is frequently not in ARISE FROM:
the proper state for analysis ➢ Personal errors made by the individual
Determinate Errors
➢ The isolation procedure usually requires analyst (e.g. inability to judge color changes
dissolution of the sample and the conversion of sharply - habitual reading of endpoints too
the desired constituent into a suitable state. late)
➢ E.g. as precipitate n gravimetric work ➢ Errors of method caused by faulty procedure
4. MEASUREMENT OF THE DESIRED CONSTITUENT (e.g. incorrect sampling, contamination of
➢ This phase of analysis constitutes the bulk of the precipitates, improper selection of
student work in analytical chemistry indicators.)
➢ Apparatus error due to poor construction or
➢ The measurement may involve determining the
calibration (e.g. inaccuracy in calibration of
weight of pure precipitate obtained from the
burette or pipettes, inequality in the length
sample (gravimetry)
of the arms of the balance, incorrect
➢ Measurement of the volume of the standard weights)
solution required to react with known quantity ➢ The degree to which information matches
of the sample (volumetric) true or accepted values
➢ Measuring a physical property that varies with ➢ Degree to which the results of a
Accuracy
(Validity)
concentration or some other variables. measurement estimates underlying true

➢ The last method generally involves the use of value.
electrometric instruments. ➢ An issue pertaining to the quality of data
5. CALCULATION AND REPORTING OF RESULT and the number of errors contained in a
➢ After analysis, the final steps involve calculating data set.
the percentage composition of the samples and ➢ Degree to which measurements fluctuates
reporting the results. around a central measurement.
(Reliability)
Precision
➢ A complete data should contain the following ➢ Precise attribute information may specify the
information. characteristics of features in great detail;
• Date however, that precise data – no matter how
• Object carefully measured – may be inaccurate.
➢ Reproducibility or repeatability.
• Reactions
➢ Denote the agreement of an experimental
• Experimental data
results or the agreement of the mean value
Accuracy & Precision
• Calculations
X of a series of experimental results with the
• Results
true value, and usually expressed in terms of
• Remarks error (accuracy).
➢ Measure of reproducibility of data w/in a
COMMON DESICCANTS series of results. Series which agree closely
• Concentrated H2SO4 with one another are said to be precise.
• CaCl2 (granular) Precise results are not necessarily accurate.
• NaOH (pellet) Precision usually reported as the average
• Silica (Silicon dioxide) deviation, standard deviation, or range.
NORIENE MAIQUEZ 7
➢ The difference between the mean and the

Absolute Error
true value.
➢ Find by dividing the absolute error by the

true value.
Relative Error
➢ Usually reported on a percentage basis by

multiplying the relative error by 100/1000
➢ Calculated by finding the differences

between individual results and the mean,
regardless of sign, adding these differences,
Deviation
Average
and dividing by the number of

determinations.
➢ Found by dividing the average deviation by

Relative average
the mean.
➢ It is usually expressed in terms of percentage
deviation
or as parts per thousand.
➢ Considered a better measure of precision

Standard Deviation
than average deviation.

➢ Acceptable for use in routine analysis.
➢ Calculated using the formula below and is
the preferred measure of precision.
➢ Other term: coefficient of variation

Relative Standard
➢ Found by dividing the standard deviation by

the mean and multiplying by 100.
Deviation
➢ The difference between the largest and

smallest results in a series of measurement.
Range
NORIENE MAIQUEZ 8
Chapter 2
pH and Hydronium-Ion Concentration in
Aqueous Systems
➢ pH and hydronium-ion concentration are a Cationic base Ag (NH3)2+
topic of considerable importance in HSO4-
pharmaceutical analysis H2PO4-
➢ many chemical reactions upon which an Anionic acids
HPO4-2
analytical procedure is based require HS-
optimum pH conditions for the reaction to
OH-
proceed to completion.
SH-
➢ Based on neutralization reactions the pH of Anionic bases
S-2
the solution at the equivalence point
determines which indicator is to be used SO4-2
form the analytical determination. Water is an amphiprotic substance and can act either
➢ When drugs such as penicillin or tetracycline as an acid or base.
are added to dextrose or sodium chloride ➢ In water system, acid properties, such as
parenteral, the quality of these solutions taste, effect on indicators, and oxidation of
changes. metals high in the electromotive series,
o Hence a new set of quality depend on the presence of the hydronium
assurance specifications is required ion, H3O+.
in order to be certain that these 2H2O ↔ H3O+ + OH-
parenteral still remain clinically ➢ Substance which on dissolving in water
acceptable. increase the concentration of hydronium
➢ The pH of admixed solutions is best ions also increase the acid properties of the
determined experimentally using a solution and are therefore acids.
standardized pH meter equipped with glass ➢ Monoprotic acids – capable of giving up
and calomel electrodes. one proton per molecule or ion
➢ When this equipment is not readily ➢ Diprotic – 2 protons
available, pH may be approximated using o The tendency of an acid to give up
pH indicator paper or by calculation. a proton is the principal determinant
(Topic 1: theory)
of the strength of the acid.
o Ex. Many of the mineral acids such
as
Bronsted-Lowry ▪ HCl
➢ According to this theory, an acid is defined ▪ HNO3
as an ionic or molecular substance capable ▪ HClO4
of giving up a proton, i.e., a proton donor. o Appear to have equal strength in
➢ A base is defined as an ionic or molecular aqueous solution, although they are
substance capable or uniting with a proton, intrinsically different.
i.e., a proton acceptor. ➢ Water is a sufficiently strong base for the
following reactions to go practically to
H2 O
completion for these acids.
H2 S
Molecular acids HCl + H2O → H3O+ + Cl-
HCl
H2SO4
NH4+ + H2O ↔ H3O+ + NH3
NH3 HSO4- + H2O ↔ H3O+ + SO4-2
Molecular bases
H2 O ➢ Leveling effect of the solvent – all strong
H3 O+ acids are leveled to the strength of the
Cationic acids same acid, H3O+ ion.
NH4+
HA + H2O → H3O+ +A-
NORIENE MAIQUEZ 9
The acetate ion, being a

CH3COOH + OH- ↔ H2O + stronger base than the
➢ Proton acceptor, or bases – when dissolved
CH3COO- water molecule, retains
in water reduce the concentration of most of its protons.
hydronium ions, as illustrated by the ff. The ammonia accepts a
OH- + H3O+ ↔ 2H2O H2O + NH3 ↔ NH4 + +OH-
proton from the water
molecule to form the
NH3 + H3O+ ↔ NH4+ + H2O acidic ammonium ion.
SO4-2 + H3O ↔ HSO4- + H2O
➢ Monoprotic – those bases which can ➢ The degree of acidity or alkalinity of a
accept one proton solution can be defined in terms of its
➢ Diprotic – those which can accept 2 concentration of hydronium or hydroxide
protons. ions.
➢ The stronger the base is, the greater its ➢ Solutions which have a hydrogen-ion
tendency to accept protons. concentration greater than 10-7 are acidic.
➢ Protolysis – the process whereby a proton is ➢ Those which have a hydrogen-ion
transferred from one molecule to another. concentration less than 10-7 are alkaline.
➢ Protolysis Reaction – reaction
➢ Since a water molecule may donate or Note:
accept a proton, it is both an acid and a ➢ To avoid the disadvantage of employing a
base. dual definition system, it is customary to use
o Two molecules may interact to form only the hydrogen-ion concentration to
ions: H2O + H2O ↔ H3O+ + OH- characterize a solution whether it is acidic,
➢ Autoprotolysis/Autoprotolysis Reaction – neutral, or alkaline – the hydroxide-ion
when there is simply a transfer of a proton concentration being implied.
from one molecule to another identical
molecule. (Topic 2: pH value)
➢ An acid and a base related to each other
so that one is formed from the other by the ➢ The reaction (acidity, alkalinity, or
gain or loss of a proton are said to be neutrality) of a solution may be defined not
corresponding or conjugate base to one only in terms of molar concentration of
another. hydrogen ions, a number frequently so small
o Cl- is conjugate base of HCl as to be quite cumbersome, but also as a
o CH3COO- is the conjugate base of pH value, a system suggested by Sorensen.
CH3COOH ➢ An important factor in this relationship is the
o NH3 is the conjugate base of the logarithm of the reciprocal of the hydrogen-
acid NH4+ ion activity, knows as the pH value or simply
o Similarly, HCl is the conjugate acid of as pH
Cl- ➢ pH is defined as the logarithm of the
o CH3COOH is the conjugate acid of reciprocal of the hydrogen-ion activity (also
CH3COO- as the negative logarithm of the hydrogen-
o NH4+ is the conjugate acid of NH3 ion activity) and is expressed as:
➢ A proton does not tend to leave an acid 𝟏
unless a base is present to accept the pH = log = log (1) – log aH+ = − log aH+
𝒂𝑯+
proton. ➢ to simplify calculations involving hydrogen
➢ Fundamental acid-base relationships. ions, we will deal only in terms of the molar
o Acid ↔ H+ (proton) + base concentration.
➢ The transfer of a proton from an acid results 𝟏
in the formation of a new acid and a new pH = log = − log [H+]
[𝑯+]
base: ➢ the concentration of other chemical
o Acid + base ↔ acid’ + base’ species present in solution may also be
The weakly basic chloride expressed in terms of the negative logarithm
ion loses its proton in HCl of their concentrations.
HCl + H2O → H3 O+ + Cl-
to the more strongly basic
o For example:
water molecule.
NORIENE MAIQUEZ 10
▪ The hydroxyl-ion • Perchloric acids

concentration may be (HClO4)
defined as the logarithm of Strong Diprotic Acid • Sulfuric acid (H2SO4)
the reciprocal of [OH-], o In an aqueous medium, HCl
called pOH. The molecules react completely with
mathematical expression for water molecules to form hydronium
this term is given as: and chloride ions. This reaction is
𝟏
pOH = log = − log [OH-] represented by the ff equation:
[𝑶𝑯−]
HCl + H2O → H3O+ + Cl−
➢ In a similar manner Kw may be defined in
terms of the logarithm of the reciprocal of ➢ The hydronium-ion concentration which
the ion-product constant of water, called forms as a result of this reaction enters the
pKw. equilibrium reaction of water.
𝟏 [H3O+] [OH−] = Kw
pKw = log = − log 10-14 = 14
𝑲𝒘 ➢ The total hydronium-ion concentration in an
➢ Taking the logarithm of both sides and aqueous solution of a strong monoprotic
changing the signs of both sides of the acid is equal to the sum of the molar
equation, the following relation results: concentration of an acid plus the molar
− log [H+] – log [OH-] = − log Kw concentration of hydronium ions
contributed by the protolysis (dissociation)
of water.
pH + pOH = pKw
➢ To determine total hydronium-ion
Topic 3: identification of concentration in ant solution, it is most
exact to employ the electroneutrality rule.
(acidic & basic organic)

➢ Simply states that a given solution is
electrically neutral, and therefore total
positive charges must equal total negative
functional group charges,
Topic 5: Ph calculation for

➢ Before the hydronium- or hydroxyl-ion
concentration of a solution containing an
organic medicinal agent can be
calculated, it is first necessary to determine (strong bases)
if the agent is an acid, base, or neutral
substance. ➢ Strong bases may be defined as proton
➢ One must be able to predict, based on acceptors whose chemical reaction with
inspection of functional groups within a water proceeds to virtual completion with
given Structural formula, if a medicinal the formation of hydroxyl ions.
agent is acidic, basic, or neutral. o Example: Guanidine is an example
o If the agent is acidic or basic, one of a strong organic base which
must then be able to determine if reacts with water to form hydroxyl
the medicinal agent is a strong or ions:
weak acid or base.
Topic 4: Ph calculation for strong

➢ Sodium hydroxide, potassium hydroxide,
(acids) and quaternary ammonium hydroxides are
strong bases simply because they
➢ Strong acids may be defined as proton completely dissociate in water to form
donors whose chemical reaction with water equal molar quantities of hydroxyl ions, the
proceeds to virtual completion with the strongest base which may exist in aqueous
formation of hydronium ions. system.
Strong Monoprotic • Hydrochloric (HCl) ➢ The principle of discussed under pH
Acids • Nitric (HNO3) calculation for strong acids apply also to
strong bases.
NORIENE MAIQUEZ 11
o To calculate the pH of a strong base • Clearing fractions by multiplying both sides

it is easier first to determine the pOH [H3O]2 = Kw + Ka [HA]
and then to subtract this value from
[H3O] = √𝑲𝒘 + 𝑲𝒂 [𝑯𝑨]
pKw.
➢ Since Kw (10−14) is usually much smaller than
Topic 6: Ph calculation for weak the product Ka [HA], it may be dropped.
Equation above then becomes:
(acids) [H3O] = √𝑲𝒂[𝑯𝑨]
➢ Weak acids may be defined as proton

Weak Acids, Charged Chemical
donors whose chemical reaction with water Species which are Cations of Salts
does not proceed to completion and of Weak Bases and Strong Acids
therefore produces a relatively small ➢ Examples of this type of acid are:
increase in the hydronium-ion o Procaine hydrochloride
concentration. o Chlorpromazine hydrochloride
➢ Weak acids may be uncharged chemical o Ephedrine hydrochloride
species such as ➢ Sulfate salts of these organic bases also fall
o Nicotinic Acid into this category, as well as other related
o Penicillin G salts.
o Acetic Acid ➢ The derivation of equations which may be
➢ Or they may be charged species, such as used to calculate the hydronium-ion
the cationic portion of salts of weak bases concentration and pH of a weak acid
and strong acids (R3NH+ Cl−) which consists of the cationic portion of salts
Weak Acids, Uncharged Chemical of weak bases and strong acids, R3NH+ Cl−,
involves the ff equilibrium reactions.
Species, HA
➢ The derivation of equations which may be
used to calculate the hydronium-ion
concentration and pH of a weak acid
which is an uncharged chemical species
involves the ff. equilibrium reactions.
2H2O ↔ H3O + OH Kw = [H3O][OH]
[𝐇𝟑𝐎][𝐀]
HA + H2O ↔ H3O + A− K[H2O] =Ka =
[𝐇𝐀]
Where K = equilibrium constant ➢ It is important to recognize that the anions of
these salts do not react with water
Ka = ionization constant of weak acid
appreciably, and therefore do not affect
[HA] = molar concentration of un-ionized the pH of dilute solutions.
acidic species ➢ Inspection of equilibrium reaction shows
[A] = molar concentration of ionized that each ion of R3NH+ which reacts with
species, the conjugate base water generates one hydronium ion and
➢ It is our objective to derive an equation one molecule of the conjugate base, R3N.
which will permit the calculation of the o If we assume that the contribution
hydronium-ion concentration in terms of Ka water makes to the total hydronium-
and C, the analytical concentration of the ion concentration is negligible, and
weak acid. that equilibrium position for reaction
➢ If the electroneutrality rule is employed, the lies almost completely to the left.
hydronium-ion concentration of a weak [H3O] = [R3N]
acid in an aqueous solution is found to the Substituting [H3O] for [R3N]
ff. relationship:
[𝑯𝟑 𝑶]𝟐
[H3O] = [OH] + [A] Ka =
[𝑹𝟑 𝑵𝑯]
Let C equal the analytical concentration of the salt
𝐊𝐰 𝐊𝐚 [𝐇𝐀]
[H3O = + C = [R3NH] + [R3N]
[𝐇𝟑𝐎] [𝐇𝟑𝐎]
NORIENE MAIQUEZ 12
Rearranging and substituting
Clearing fractions by multiplying both sides by OH

gives
Weak Bases, Charged Chemical

Topic 7: Ph calculation for weak Species which are anions of salts of
Strong Bases and Weak Acids
(bases) ➢ Examples of this type of base are:
o Sodium sulfadiazine
➢ Weak bases may be defined as proton
o Sodium acetate
acceptors whose chemical reactions with
o Potassium penicillin G
water do not proceed to completion and
o Sodium pentobarbital, etc.
therefore produce a relatively small
➢ The derivation of equations which may be
increase in the hydroxyl-ion concentration.
used to calculate the hydroxyl-ion
• Ammonia concentration, pOH, and pH of a weak base
• Atropine
Uncharged Weak Bases which consists of the anionic portion of salts
• Morphine
• Chlorpromazine etc. of strong bases and weak acids, Na+ A-,
• Acetate ion
involves the ff. equilibrium reactions.
• Barbiturate ion
• Sulfonamide anion
Charged chemical Weak
• Penicillin anion
Bases
• Other anionic ions of
salts of weak acids and
strong bases (Na+ A-)
Weak Bases, Uncharged (Topic 8: salts)

Chemical Species, R3N ➢ Salts may be defined as those chemical
➢ The derivation of equations which may be products other than water which are
used to calculate the hydronium-ion obtained from the neutralization of
concentration and pH of a weak base equivalent amounts of
which is an uncharged chemical species 1. A strong acid and a strong base
involves the ff. equilibrium reactions. 2. A weak base and a strong acid
2H2O ↔ H3O + OH Kw = [H3O][OH] 3. A strong base and a weak acid
4. A weak acid and a weak base
➢ It is important to point out:
[𝑹𝟑 𝑵𝑯][𝑶𝑯]
R3N + H2O ↔ R3NH + OH K[H2O] = Kb = a. That the pH of a salt solution
[𝑹𝟑 𝑵]
obtained by dissolution of the
Where K = equilibrium constant crystalline form of a salt, such as:
Kb = ionization constant of weak base sodium acetate, is the same as that
[R3N] = molar concentration of un-ionized obtained during the neutralization
base reaction of chemically equivalent
[R3NH] = molar concentration of ionized quantities of acid and base
species, the conjugate acid b. That salts exist in solution as ions.
NORIENE MAIQUEZ 13
pH Calculation for a Salt Solution of the weak acid (acetic acid and
sodium acetate) or a weak base
a Strong Acid and a Strong Base
and some salt of weak base
➢ Examples of this type of salt are: (ammonia and ammonium
o Sodium chloride chloride).
o Potassium sulfate ➢ The derivation of the pH equation of a
o Sodium nitrate buffer solution of a weak acid and some
➢ In dilute solutions salts of this kind do not salt of the weak acid will be illustrated using
affect the equilibrium reaction of water, and acetic acid and sodium acetate.
therefore the pH may be considered the
same as that of water, 7.00.
pH Calculation for a Salt Solution of
a Weak Base and a Strong Acid
➢ Examples:
o Ammonium chloride
o Atropine hydrochloride ➢ In any aqueous solution in which two or
o Chlorpromazine hydrochloride more equilibrium reactions take place in the
o Ephedrine sulfate same flask, there is but one hydronium-ion
➢ In salts of this nature the cationic portion is concentration which affects all the
considered the weak acid as defined by equilibrium reactions involving hydronium
the Bronsted-Lowry theory and reacts with ions.
water to generate hydronium ions. ➢ It is well to recognize also that the salt in the
pH Calculation for a Salt Solution of buffer solution is the conjugate base of the
acid, and a useful relationship can be
a Weak Acid and a Strong Base observed.
➢ Examples:
o Sodium acetate
o Potassium penicillin
o Sodium sulfamethazine
➢ In salts of this kind the anionic portion of the ➢ Taking the logarithm of both sides of this
salt is considered the weak base, as defined equation and changing signs gives:
by the Bronsted-Lowry theory of acids and
bases, and reacts with water to generate
hydroxyl ions.
pH Calculation for a Salt Solution of
➢ Equation above permits the calculation of
a Weak Acid and a Weak Base the pKb value of a conjugate base if the
pKa value of the acid is known, and vice
versa.
Topic 10: Ph calculation for weak

(Topic 9: buffer solution)
➢ Buffer solutions have the property of (polyprotic acids)
resisting changes in pH when acids or bases
➢ Acids with more than one acidic hydrogen
are added to them.
per molecule react with water in a stepwise
o This property of resisting pH changes
manner.
usually results from the presence of a
o The protolytic reactions involved
pair of chemicals, often referred to
and the chemical equilibrium
as a buffer pair, which consists of
expressions for a diprotic acid, H2A,
either a weak acid and some salt of
are as follows:
NORIENE MAIQUEZ 14
be calculated using the ff.

mathematical equation.
[𝑨]𝒙 𝟏𝟎𝟎
Percent ionization =
𝑪
➢ Solutions of polyprotic acids contain varying Where [A] = molar concentration of conjugate
quantities of chemical species involved in acid or conjugate base
the respective equilibrium reactions. C = analytical concentration of the acid or
➢ For all practical purposes a weak diprotic base.
acid with Ka1 value about 200 times greater
than Ka2 may be treated as a monoprotic
acid so far as calculations of the hydronium-
ion concentration are concerned.
Topic 11: Ph calculation for weak
(polyprotic bases)
➢ Bases with more than one basic functional
group per molecule react with water in a
stepwise manner.
o The protolytic reactions involved
and the chemical equilibrium
expressions for a diprotic acid,
R2NCH2CH2NR2, are as follows:
➢ Solution of polyprotic bases contain all

chemical species involved in the chemical
equilibrium reactions.
Topic 12: degree of
(Ionization)
➢ The degree of ionization or protolysis of
weak acids (or weak bases) is defined as
the fraction of the analytical concentration
of weak acid (or base) which is in the
ionized form.
o The degree of ionization is a function
of the ionization constant K and the
analytical concentration C and may
NORIENE MAIQUEZ 15
Chapter 3
Principles of Titrimetric (Volumetric)
Analysis
Titration may be conducted by direct
Topic 1: definition of
➢
titration as in assay of HCl using NaOH as the
titrant, or they may be conducted by
(terms) residual titration as in the assay of zinc
oxide.
Defined as those analytical methods in ➢ Results in drug assays are usually expressed
which the volume of solution of known in terms of % w/w, % w/v and % v/v as
concentration consumed during an described in the official compendiums.
analysis is taken as a measure of the
amount of active constituent in a sample
➢ In titrimetric analysis it is convenient to use
Titrimetric Methods
being analyzed. equivalents for calculation purposes.

• Ex. HCl is assayed by weighing a ➢ Single most important principle which must
sample accurately and carefully be understood regarding equivalents is that
adding a solution of known 1 equiv of an acid neutralizes exactly 1
concentration of sodium hydroxide equiv of a base, and vice versa.
in the presence of suitable indicator
o 1 equiv of an oxidizing agent reacts
until equivalent amounts of NaOH
and HCl have reacted. with exactly 1 equiv of a reducing
HCL + NaOH → NaCl +H2O agent, and vice versa.
➢ In general, an equivalent is the quantity of a
substance that is chemically equivalent to
1.0079 g of hydrogen or hydrogen-ions.
Constituent
Analyte or
Active
The chemical substance being analyzed o Ex.

o I mol of 36.46 g of HCl and 0.5 mol or
49.035 g of H2SO4 contains 1.0079 g
of hydrogen ions (1 equiv) and is
Defined as the solution of known capable of neutralizing exactly 1
Titrant
concentration and usually added by mol (1 equiv) or 40.00 g of NaOH or

means of a burette. 0.5 mol or 85.675g of Ba(OH)2
Definitions
Titration
The act of adding and measuring the • The gram-equivalent of a chemical is

volume of titrant used in the assay defined as the weight in grams which is
Gram-equivalent weight
chemically equivalent to 1 gram-atom

of hydrogen (1.0079g).
Usually, a chemical which changes color • In neutralization reactions it is
Indicator
(GEW)
at or very near the point in the titration defined as the weight of a

where equivalent quantities of analyte substance in grams which
and titrant have reacted. 1. Contains
2. Furnishes
3. Reacts with directly or indirectly
Stoichiometric
Equivalence
4. Replaces 1 gram-atom or ion

point or
Theoretical point at which equivalent of hydrogen.

point
amounts of each have reacted.

milliequival
ent weight
(GmEW)
Gram-
Defined as GEW/1000. This term is used

quite frequently in titrimetric calculations.
The titration is actually stopped at some
point. Which there occurs a sudden
End point
change in some property of the reaction

mixture, a change which is made
apparent by use of indicators or
electrometrically.
NORIENE MAIQUEZ 16
➢ Thus, a solution of HCl may be standardized

Equivalent
Defined as the number of gram-

titrimetrically using a standard solution of
equivalents involved in a quantitative
procedure. sodium hydroxide as a secondary standard
or using a sample of sodium carbonate of
known purity as a primary standard.
Milliequivalent
Defined as the number of gram- Topic 2: Chemical reactions used

(meq)
milliequivalents involved in a quantitative

procedure.
(in titrimetry)
➢ The four types of chemical reactions which
Standard
Solution
serve as the basis of titrimetric analysis are:

Solution of known normality or molarity.
1. Neutralization (acid-base) in
aqueous and non-aqueous
• A concentration expression and is
solvents
defined as the number of equivalents of o Carried out with solution
Normality
solute per liter (equiv/liter) or (solvent + solute)

milliequivalents per milliliter (meq/mL) of o Aqueous (solvent + H2O)
solution. 2. Oxidation-reduction (REDOX) –
• Solution w/c contains an equivalent
weight of a solute in a liter of solution
gain or loss of electron
3. Precipitation – produces
• An expression of the concentration of a precipitate
Molarity
solution in terms of moles per liter. 4. Complexation – produces

• Solution w/c contains a molar mass of
solute per liter of solution. complex product
➢ Regardless of the type of reaction used,
however, four requirements must be met if
Standardization
• The determination of the normality of

the reaction is to be used for titrimetric
molarity of a solution
• Process of determining the accurate analysis.
concentration of roughly prepared of ➢ They are:
standard solution. 1. The reaction must proceed to
completion, that is the chemical
equilibrium constant K must be
Secondary
equal to a greater than 108

Standard
May be accomplished by the use of

another standard solution 2. The reaction must proceed in a
stoichiometric manner
3. A suitable end-point-detecting
device (chemical indicators,
Standard
Primary
By the use of a carefully weighed sample electrode, etc.) must be

of a substance of known purity available.
4. For direct titrimetric methods the
reaction must be rapid so a
Defined as the weight of a substance sharp end-point is discernible.
Titer
chemically equivalent to 1 mL of a
standard solution.
Common Primary Standard Used for Acids

1. Anhydrous sodium carbonate
2. Calcium carbonate
3. THAM (Trihydroxymethylamino methane)
Common Primary Standard Used for Bases
4. Sulfamic acid (H3NO3S)
5. Benzoin Acid (C6H5COOH)
6. Potassium Biphthalate KHP (KHC8H4O4)
NORIENE MAIQUEZ 17
Topic 3: Titrimetric analysis

1. To determine the end points in
neutralization processes
2. To determine hydrogen-ion
based on neutralization 3.
concentrations [H+] or pH
To indicate that a desired change in
pH has been effected.
(reactions) ➢ This organic substance may be acids or
bases themselves, capable of existing in two
➢ Illustrated using methods based on forms of different color that are mutually
neutralization reactions. convertible, one into the other, at given
➢ Basic principle, general calculations and hydrogen-ion concentrations.
laboratory procedures employed for 1. The physicochemical theory attributes the
titrimetric method based on neutralization color to certain ions an increase in which
reactions also apply to titrimetric methods causes the appearance of a new color, and
based on other chemical reactions. a decrease in which causes the
disappearance of a color or the
Neutralization Reactions
appearance of a different color.
➢ Chemical process in which an acid (proton 2. The organic theory attributes the color of
donor) reacts with a base (proton acceptor) indicators to certain groupings of the
➢ The products of a neutralization reaction in elements in a compound, and the change
aqueous solution are water and a salt, in color to a change in molecular structure.
o e.g., NaCl 3. The colloidal theory assumes that indicators
o sodium acetate form colloidal solutions the change in color
o NH4Cl, etc., depending upon the of which is dependent upon change in size
acid and base used in the reaction. of the colloidal particle.
The point at which an indicator changes
Strong Acid and Strong Base
➢
color in any given titration is dependent on
(Also Applies Vice Versa)

the hydrogen-ion concentration of the
solution and may not be indicative of the
absolute neutrality or completion of a
reaction.
Color Color
Change Change
pH pH
Canceling Na+ and Cl- Indicator Acid Base
Range Range
Malachite green Yellow 0.0 Green 2.0
Methyl yellow Red 2.9 Yellow 4.0
Bromophenol
Yellow 3.0 Blue 4.6
blue
For a weak organic base such as ephedrine the Methyl orange Pink 3.2 Yellow 4.4
equilibrium-constant expression is Bromocresol
Yellow 4.0 Blue 5.4
green
Methyl red Red 4.2 Yellow 6.2
Bromocresol
Yellow 5.2 Purple 6.8
purple
Rearranging Bromothymol
Yellow 6.0 Blue 7.6
blue
Phenol red Yellow 6.8 Red 8.2
Cresol red Yellow 7.2 Red 8.8
Thymol blue Yellow 8.0 Blue 9.2
Phenolphthalein Colorless 8.0 Red 10.0
Indicators thymolphthalein Colorless 9.3 Blue 10.5
➢ Complex organic compounds used
NORIENE MAIQUEZ 18
Indicator Concentration Solvent

Rules for the Use of Indicators Bromocresol
50 mg 100 mL alcohol
1. Use 3 gtts of indicator test solution for a green
titration unless otherwise directed 20 mL 0.05N NaOH
Bromocresol
2. When a strong acid is titrated with a strong 250 mg diluted with H2O to
purple
250mL
alkali, or a strong alkali with a strong acid,
Bromocresol
methyl orange, methyl red, or 100 mg 100mL diluted alcohol
Blue
phenolphthalein may be used.
26.2mL 0.01N NaOH
3. When a weak acid is titrated with a strong
Cresol red 100 mg diluted with H2O to
alkali, use phenolphthalein as the indicator 250mL
4. When a weak alkali is titrated with a strong Cresol red- 15mL thymol blue and
acid, use methyl red as the indicator Thymol blue 5mL cresol red
5. A weak alkali should never be titrated with Methyl orange 100 mg 100mL H2O
a weak acid, or vice versa, since no Methyl red 100 mg 100mL alcohol
indicator will give a sharp end point.
Methyl red- Equal parts methyl red
6. The appearance of a color is more easily methylene blue and methylene blue
observable than is the disappearance.
Phenol red 100 mg 100mL alcohol
Therefore, always titrate where possible to
Phenolphthalein 1 mg 100mL alcohol
the appearance of a color.
Thymol blue 100 mg 100mL alcohol
Mixed Indicators thymolphthalein 100 mg 100mL alcohol
➢ The criteria of a good indicator for Standard Solutions

analytical purposes are that there will be a ➢ The concentrations of standard solutions
sharp contrast between the two colors can be expressed in terms of
which it exhibits in acid and alkaline o Normality, or the number of
mediums and that the change in color will equivalents of solute per liter of
take place over a very small range of pH solution (milliequivalent per milliliter).
values. o Molarity, or the number of moles of
➢ Some indicators do not give a sharp color solute per liter of solution
change o Molality, or the number of moles of
o Methylene Blue + Methyl Red = Gray solute per 1000g of solvent
Color ➢ Tenth-normal solution of HCl, also
o Xylene Cyanol + Methyl Orange designated 0.1N or N/10, contains 0.1 equiv
o Bromocresol Green + Methyl Red or 0.1 equiv weight. 3.646g of HCl per liter,
o Bromocresol Green + Chlorophenol or 0.1 meq. 3.646mg, per milliliter.
Red ➢ Twentieth-Molar (0.05M) solution of H2SO4
o Cresol Red + Thymol Blue contains 0.05 mol or 4.904g of H2SO4 per
o Thymol Blue + Phenolphthalein liter.
Sensitivity of Indicator Solutions

➢ The importance of a correct evaluation of
equivalents in terms of mole fractions or
➢ Indicator solutions should be tested for grams in all calculations involving standard
sensitivity. solutions may be seen in the ff. examples:
o Done by adding 0.5mL of indicator 1. The preparation of 1 liter of N H2SO4
solution to 25mL of carbon dioxide- requires 49.04g of H2SO4, since 1 equiv
free distilled water and titrating the of H2SO4 is needed and since 1 mol or
resulting solution with 0.02N alkali or 98.08g of H2SO4 is 2 equiv.
acid. 2. Ten percent H2SO4 is 1.02 M or 2.04 N,
o Upon the addition of 0.25mL of the since 1 liter contains 100g, 100/49.04 =
standard alkali or aid solution, the 2.04 equiv, or 2.04/2 = 1.02mol.
respective characteristic color 3. Each mL of 0.1N H2SO4 is equivalent to
should develop. 1.703mg of NH3, since each mL of the
solution contains 0.0001 equiv of H2SO4,
which is equivalent to 0.0001 x 17.03 =
0.001703g or 1.703mg of NH3.
NORIENE MAIQUEZ 19
o In this example, typical of the ➢ The standard alkali solutions commonly

calculation of the titer of a used are
solution, 17.03g was taken as the o Sodium hydroxide
equivalent weight of NH3 for the o Potassium hydroxide
reason indicated by the ff. o Barium hydroxide
equation: o These solutions absorb carbon
NH3 + H+ → NH4+ dioxide from the air, thereby
17.03 changing rapidly in concentration
o Sodium and potassium hydroxides
Calculations in Volumetric Analysis may become contaminated with
➢ Interpretation of the data obtained in carbonates that impair their
volumetric analysis is facilitated usefulness because of the liberation
considerably by the use of the meq wt. of carbon dioxide during acid-alkali
factor corresponding to the gravimetric titration.
factor used in gravimetric analysis o Barium hydroxide solutions remain
o Defined as the weight of substance free from carbonates, since
chemically equivalent to 1mL of a 1 absorbed carbon dioxide is
N solution. precipitated as insoluble barium
➢ The exact normality of the solution carbonate
employed, usually expressed to the 4th ➢ Alkali solutions should be prepared
decimal place, must, however, be known. carbonate-free, and they should be
o For example, 50.0mL sample of protected from carbon dioxide by means of
Ca(OH)2 solution required 19.50mL of soda-lime absorption tubes.
a 0.1050N HCl solution to neutralize o Should be restandardized frequently.
it. Calculate the amount of Ca(OH)2
in 100mL of the solution (%w/v). Topic 4: titration
Ca(OH)2 + 2HCl → CaCl2 + 2H2O (curves)

➢ The manner in which the pH of a solution
19.50 x 0.1050 x 0.03705 = g of Ca(OH)2 per 50mL changes during a titration is best shown by
sample preparing a graph in which the pH value is
plotted on the y axis and the volume of the
100 titrant is plotted on the x axis
19.50 0.1050 x 0.03705 x = 0.152g per 100mL
50 ➢ May be prepared from pH data obtained
A general formula which can be used for the experimentally, or the data for the graph
calculation of the percent purity of a sample may be calculated.
determined by the direct titration is ➢ In actual practice, however, pH
measurements are made experimentally,
and titration curves and their derivatives are
𝑚𝐿 𝑥 𝑁 𝑥 𝑚𝑒𝑞 𝑤𝑡. 𝑥 100 𝑤 𝑤 used for the purpose of determining end
= % 𝑜𝑟 %
𝑠𝑎𝑚𝑝𝑙𝑒 𝑤𝑡. 𝑜𝑟 𝑣𝑜𝑙. 𝑤 𝑣 points for titrimetric assays.
o The titration curve is that portion
➢ The standard acid solutions used in where the slope of the curve is
acidimetry and alkalimetry are usually steepest and is commonly referred t
prepared from hydrochloric or sulfuric acid. as the break in the titration curve.
o HCl is preferable to the H2SO4 in the ➢ An indicator is used to detect the
titration of compounds that yield a equivalence point, it must give a sharp
precipitate with the latter, discernible color change at that point in the
▪ Such as: titration; otherwise, the color change may
• Barium hydroxide lead to erroneous results.
o Sulfuric acid, Is preferable in hot ➢ The preparation of a titration curve is not
titrations, since there would be difficult if one realizes that the calculations
danger of loss of hydrochloric acid are based on only four types of points,
due to volatilization. which correspond to:
NORIENE MAIQUEZ 20
1. The pH of the solution being titrated but ➢ Many medicinal agents, such as alkaloids,
before any titrant is added and other free amine compounds react
2. The pH of the solution after titrant is similarly.
added but before the equivalence point
is reached
Titration Curve of Sodium
3. The pH at the equivalence point Carbonate Using HCl as Titrant
4. The pH beyond the equivalence point.
Titration of a Strong Acid Using a
Strong Base
➢ In this type of titration, a strong acid, such as ➢ For this titration phenolphthalein, methyl red,
HCl, is titrated with NaOH, a strong base. or methyl orange may be used as the
o HCl – Strong Acid indicator.
o NaOH – Strong Base ➢ One equivalent of hydrogen is consumed at
➢ It must be clearly understood that these the phenolphthalein end point, and 2 equiv
calculations apply only for strong acid-
of hydrogen is consumed at the methyl red
strong base titrations and methyl orange end point.
➢ Weak acid-strong base titrations and weak
base-strong acid titrations require different Indicators
calculations at these for regions or points in
➢ Indicators used in assays based on
the titration curve.
neutralization reactions may be classified as
Titration of a Weak Acid Using a weak organic acids and bases.
Strong Base ➢ Only the weak organic acid type of
indicator will be considered
➢ In this type of titration, a weak acid such as
➢ The principles may be applied equally well
acetic acid is titrated with NaOH, a strong
to indicators which are weak organic bases.
base.
➢ The chemical properties upon which the
o Acetic Acid – Weak Acid
action of an indicator depends are that
o NaOH – Strong Base
1. The color of the ionic species of an
➢ Observe that phenolphthalein is a suitable
indicator is diff. from that of the
indicator for this titration, because a sharp
undissociated species,
color change is obtained at the
2. The color the indicator imparts to a
equivalence point (20mL of titrant).
solution depends on the relative
➢ Methyl red, is unsuitable, because the color
concentration of ionic and
change is too gradual, beginning at about
undissociated species in solution
3mL and finally changing to yellow at about
3. The relative concentrations of the ionic
19mL.
and undissociated species in solution
Titration Cure of a Strong Base depend on the hydronium-ion
(NaOH) Using a Strong Acid (HCl) concentration.
➢ An important conclusion which may be
➢ The pH calculations are identical with those
drawn from this discussion is that the
used in the titration of a strong acid and a
minimum change in pH required for an
strong base, only the order is reversed.
indicator to change from one perceptible
o Again, either phenolphthalein or
color to another (red to yellow in this
methyl red may be used as an
example) is two pH units.
indicator.
➢ The pH range through which an indicator
Titration Curve of a Weak Base must pass to change from one distinct color
to another is known as the transition range.
(NH3) Using a Strong Acid (HCl) ➢ It is also very important to recognize that in
➢ This curve demonstrates graphically the pH order to obtain a sharp end point (a distinct
changes which take place during the color change) during a titration in which an
titration of ammonia. indicator of this type is used, 1 gtt of titrant
must bring about a minimum change of at
least two pH units.
NORIENE MAIQUEZ 21
Chapter 4
Acidimetric Analysis
be in excess and titrating the excess of the
Topic 1: definition of latter with another std solution.
(Terms) Topic 3: Nitrogen Determination

➢ Acidimetry, the direct or residual titrimetric (by the Kjeldahl Method)
analysis of bases using an accurately
measured volume of acid, is supplied in ➢ It frequently happens that ammonia is not
the analytical control of a considerable quantitatively liberated from an organic
number of official substances, both nitrogen-containing compound by acid or
alkaline hydrolysis as previously described.
inorganic and organic.
➢ The nitrogen of such a compound is in
Conducted by introducing a trivalent state, amino or amido nitrogen,
standard acid solution gradually
an equivalent amount of ammonia can be
from a burette into a solution of
the base being assayed until
obtained as ammonium sulfate by
Direct Titration digestion of the sample with concentrated
chemically equivalent amounts of
each have reacted as shown by sulfuric acid until decomposition is
some change in properties of the complete as indicated by the
mixture. disappearance of carbon which is
• Used whenever the end point of converted to carbon dioxide during the
a direct titration deviates digestion.
appreciably from the o The ammonia is liberated by
stoichiometric points for some treatment of the residue of
reason ammonium sulfate and excess
• e.g., when the basic sample is sulfuric acid with sodium
insoluble in water and the rate
Residual hydroxide, and distilled into excess
of its reaction with the std acid
Titration boric acid.
is relatively slow.
• Basic sample is treated with an ➢ The distillate in each case is titrated in the
amount of standard acid known usual manner.
to be excess of a chemically ➢ Time required for the digestion can be
equivalent amount, and the reduced by adding potassium sulfate or
excess acid is subsequently anhydrous sodium sulfate in a sufficient
titrated with a std base. amount so that the molal ratio of H2SO4 to
K2SO4 is 1.5, thereby raising considerably
Topic 2: residual titration the temperature at which the digestion is
carried out (GUNNING MODIFICATION).
(methods) o Can also be reduced by addition
of catalysts such as copper sulfate
➢ Residual titration or back titration is or selenium.
frequently used when a reaction proceeds ➢ If all or part of the nitrogen is present as
slowly or when the substance to be nitrate, a further modification is necessary.
assayed does not give a distinct, sharp ➢ Salicylic acid is added to the digestion
end point with an indicator by direct mixture; by its reaction with nitric acid
titration. liberated by the sulfuric acid, it forms
➢ Carried out by dissolving the substance nitrosalicylic acid and prevents loss of the
under examination in an accurately nitric acid along with other volatile
measured quantity of std solution known to substance formed during the digestion.
NORIENE MAIQUEZ 22
Chapter 5
Alkalimetric Analysis
➢ Acids are estimated quantitatively by ➢ Ester, acid anhydrides, acid chlorides, and
methods analogous to those employed aldehydes – some classes of compounds
form the quantitative estimation of bases, found in this group.
viz., by directly titrating an exact quantity
of the acid, acid salt, or other acidic
substance with std alkali solutions or by
adding an excess of the latter and
determining the amount in excess by
residual titration with std acid solution.
o It requires only one std solution, the
std base, and fewer measurements
of volume.
➢ In assaying acid, the quantity of acid to be
taken should be such that about 30 to 40
mL of the std base will consumed.
➢ It is recommended that the normality of
the solution obtained by dissolving the
acid sample be approximately the same
as that of the titrant.
o Except when otherwise directed,
the liquid to be titrated should be
brought to room temperature
before titration
➢ Most inorganic acids,
o Methyl red or phenolphthalein –
used as indicator
o Alkali should be standardized with
the particular indicator used.
➢ Most organic acids,
o Phenolphthalein – frequently used
indicator
o Thymol blue, bromothymol blue
and thymolphthalein – are also
employed.
Topic 1: residual titration
(method)
➢ Used whenever direct titration methods
are not practicable.
➢ Method is applied to those official
compounds which react too slowly with
the titrant because of poor solubility.
➢ Heating process – used or precipitation
method is employed to convert the
substance for reaction with the std base.
NORIENE MAIQUEZ 23
Chapter 6
Non-Aqueous Titrimetric Analysis
Hydronium ion
Topic 1: properties of drugs that are
➢
o The least protophilic substance in
aqueous solutions formed from the
assayed thru nonaqueous titrimetry reaction of acid and water
➢ Poorly soluble in water Notes

➢ Weakly reactive in water ➢ Contrary to the Arrhenius concept that
Notes neutralization is a reaction between
hydrogen ions and hydroxide ions in
➢ The amine salts had to be converted to
aqueous solutions of acids and bases
the water-soluble free base, extracted
o The titration of a base with a std.
with an organic solvent, and treated with
solution of an acid, or the titration
excess standard acid
of an acid with a std. solution of a
➢ Kjeldahl Method
base
o Quantitative determination of
o When solvents other than water
nitrogen contained in organic
are employed is feasible and
substances plus the nitrogen
frequently offers certain
contained in the inorganic
advantages
compound ammonia &
➢ In aqueous solutions
ammonium.
o Neutralization may be interpreted
➢ Moisture is to be avoided in nonaqueous
as a reaction between proton
procedures
donors and proton acceptors
o Because water can act as a weak
▪ i.e., acids and bases,
base and compete with the weak
respectively.
nitrogen base for perchloric acid
➢ In nonaqueous solvents,
during titration.
o It frequently becomes necessary to
➢ Moisture content
regard neutralization as a reaction
o <0.05%
between weakly protophyllic
➢ Organic solvents have higher coefficients
substances which tend to accept a
of expansion, thus
pair of electrons and highly
o Temperature at standardization =
protophyllic substances which tend
temperature during analysis
to provide a pair electron in the
(Topic 2: neutralization)
formation of covalent bonds by
coordination
▪ i.e., a reaction between
Aqueous Solutions Nonaqueous Solutions
acids and bases.
• Acid • Weakly protophilic ➢ Acidity decreases in the following order:
 Proton donor  Electron pair o HClO4 > HBr > H2SO4 > HCl > HNO3
acceptor
➢ Bases such as metal alkoxides become
• Base • Highly protophilic
stronger bases in nonaqueous solutions
 Proton  Electron pair
acceptor donor where these are least ionized.
➢ Mixtures of two or three components can
➢ Water is not essential for the neutralization
be titrated selectively in a single titration
reaction to take place
thru selection of the proper solvent.
➢ Acetonitrile, acetone, and
o Ethylenediamine + theophylline
dimethylformamide
▪ Ethylenediamine → acetic
o provides a greater difference in the
acid
protophilic properties of
▪ Theophylline → acetic
substances occurring in
anhydride
nonaqueous solutions
NORIENE MAIQUEZ 24
(Topic 3: end points) Acidic Solvents

• Used for weak bases • Formic acid
and their salts • Glacial acetic acid
➢ Indicators used in neutralization reactions • Utilizes the protogenic • Propionic acid
in quality of the solvent • Acetic anhydride
aqueous solutions are weak acids or bases • Sulfonyl chloride
which undergo color changes with
changes in pH.
➢ The equivalence point of a given Titrants
neutralization reaction is determined ➢ Perchloric acid in glacial acetic acid or
potentiometrically dioxane
➢ The indicator which produces the sharpest o Most valuable and widely used
color change with the least increment of titrant
volume of titrant added near the o Strongest of the known common
equivalence point is chosen acids
➢ Organic sulfonic acids
Topic 4: nonaqueous o Used to a limited extent
o Stronger than perchloric acid
(acidimetry) Indicators
➢ Weak bases which do not meet this Weak Bases and their Relatively stronger
requirement cannot be titrated with salts bases
accuracy in aqueous systems • Crystal Violet • Methyl red
o Because the solvent, water,  Methylrosaniline • Methyl orange
competes with the basic species in chloride • Thymol blue
 Produces a visual
solution for the proton of the titrant.
endpoint with less
➢ This action of water is due to its
than 0.1mL of
amphiprotic properties;
titrant at the
o It may act either as an acid or a potentiometric
base depending upon the end point
experimental conditions. • Quinaldine Red
• α-naphtholbenzein
Analyte • malachite green
➢ The following may be analyzed with
perchloric acid as the titrant:
o Amines Perchloric Acid
o Amine salts ➢ 70 to 72% in water
o Heterocyclic nitrogen compounds ➢ Specific Gravity
o Alkali salts of organic acids o 1.6
o Alkali salts of weak inorganic acids ➢ Powerful oxidizing agent
o Amino acids ➢ MW
o 100.46
Solvents ➢ The approximately 30% water in the HClO4
➢ The solvents are either relatively neutral or solution can be quantitatively converted
acidic in nature. to
➢ The choice of solvent is determined by the acetic acid by the addition of acetic
basic character of the substance to be anhydride
assayed o H2O + (CH3CO)2O → 2CH3COOH
Neutral Solvents ➢ The solution should be allowed to cool
• Either Aprotic or • Acetonitrile before adding glacial acetic acid to
Amphiprotic • Alcohols volume.
• Used for their solvency • Chloroform ➢ Solvent
action • Benzene o Glacial acetic acid
• Do not enhance • Dioxane
o Dioxane
dissociation to any • Ethyl acetate
great degree
NORIENE MAIQUEZ 25
▪ Contains reducing o All three hydrogens of H3BO3 can

substances → removed by be detected using a potentiometer
passing the solution through to determine the end points
a column of activated
alumina
Solvents
➢ Primary Standard ➢ Factors in choosing a basic solvent
o KHC8H4O4 – Δ 120°C for 2 h o Solubility of the substance to be
➢ Indicator analyzed
o Crystal violet o Relative base strength of the
➢ End Point solvent
o Violet → emerald green o The sharpness of the end point
change
𝑔 𝑜𝑓 𝐾𝐻𝐶8𝐻4𝑂4 o Nonreactivity of the solvent
𝑁= Strong Bases
(𝑉𝑏𝑙𝑎𝑛𝑘 − 𝑉𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 ) 𝑥 0.20423
❖ Used as solvents for the titration of
weak acids such as enols
➢ Gmew (KHC8H4O4) = 0.20423
o Ethylenediamine
Assay of Methacholine Chloride o n-butylamine
o Morpholine
➢ Very hygroscopic → vacuum desiccator
➢ Solvent Weak Bases
o Glacial acetic acid ❖ Used as solvents for medium-
➢ Indicator strength acidic substances
o Crystal violet o Dimethylformamide
➢ End Point o Pyridine
o Violet → blue green Notes:
➢ Mercuric acetate
❖ Strongly acidic compounds may
o Prevents the interference of the
be titrated in any of these solvents.
hydrochloric acid displaced
❖ Ethylenediamine
through the formation of the
o used as solvent for strong
relatively unionized HgCl2
acids.
Topic 5: nonaqueous ❖ Sulfonamides

o N-alkyl substituent → low
acidity → ethylenediamine
(alkalimetry) ▪ Sulfonamides which
contain an N-alkyl
➢ Many weakly acidic substances can be substituent possess
titrated in an appropriate nonaqueous low acidity, and
solvent with a sharp end point consequently
Analytes ethylenediamine is
the solvent of
➢ Acid halides
choice
➢ Anhydrides o N-phenyl or N-pyridyl →
➢ Acids relatively stronger acids
➢ Amino acids → dimethylformamide
➢ Enols ▪ Dimethylformamide
➢ Imides is the preferred
➢ Phenols solvent
➢ Pyrroles ❖ Sulfanilamide + Sulfathiazole
➢ Sulfonamides o Sulfathiazole →
➢ Organic salts of inorganic acids dimethylformamide →
➢ Boric Acid thymol blue
o Weak inorganic acid ▪ With the solvent
o Easily titrated using dimethylformamide
ethylenediamine as the solvent and thymol blue
NORIENE MAIQUEZ 26
indicator, only o H2O + CH3ONa → CH3OH + NaOH

sulfathiazole will o H2CO3 + 2CH3ONa → 2CH3OH +
react with the Na2CO3
sodium methoxide ➢ Primary standard
o Sulfonamide → butylamine o C6H5COOH dissolved in
→ azo violet HCON(CH3)2
▪ Second titration with ➢ Indicator
a sample of the o Thymol blue in HCON(CH3)2 (1 in
same size in 100)
butylamine using ➢ End point
azo violet indicator o Blue
will determine total ➢ Standard sodium methoxide solutions must
sulfonamides be restandardized frequently.
Titrants
𝑔 𝑜𝑓 𝐶6𝐻5𝐶𝑂𝑂𝐻
➢ Sodium methoxide 𝑁=
(𝑉𝑏𝑙𝑎𝑛𝑘 − 𝑉𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 ) 𝑥 0.12212
o officially used base
➢ Lithium methoxide
o preferred when sodium methoxide ➢ Gmew (C6H5COOH) = 0.12212
produces a gelatinous precipitate
➢ Potassium methoxide
Assay of Phenytoin
o stronger titrant, may produce a ➢ Organic acid whose acidity can be
gelatinous reaction product slightly enhanced in HCON(CH3)2
➢ Sodium aminomethoxide ➢ Behaves as a monoprotic acid
o strongest base ➢ Yields monosodium salts with sodium
➢ Sodium triphenylmethane methoxide
o used for weakly acidic compounds ➢ Solvent
such as phenols and pyrroles o HCON(CH3)2 – Dimethylformamide
➢ Indicator
Indicators o Azo violet in C6H6
➢ Azo violet ➢ Endpoint
o indicator of choice in the o Blue
titration of weak or intermediate
strength acids in n-butylamine Topic 6: tetrabutylammonium
solvent
➢ o-nitroaniline
o indicator used for the titration
(hydroxide)
of weak acids ➢ Drugs
➢ End point ➢ Preparation
o clear blue color for either azo
violet or thymol blue
Drugs assayed with
Sodium Methoxide tetrabutylammonium hydroxide
➢ Mole-for-mole basis
➢ Methanol – cooled in ice water
o Azathioprine
➢ Sodium metal – freshly cut and added in
o Fluorouracil
small portions
o Trichlomethiazide
o Na° + CH3OH → CH3ONa + H°↑
➢ Benzene – added to volume upon Preparation
dissolution of sodium metal in methanol ➢ 2Bu4NI + Ag2O + H2O → 2Bu4NOH + 2AgI
➢ Carbon dioxide and moisture must be ➢ Typical acid base indicators are used to
avoided because of the following detect the end points.
reactions which may result to instability
and turbidity:
NORIENE MAIQUEZ 27
Chapter 7
Precipitation and Complexation Methods
of Analysis
Topic 1: precipitation 2. Potassium chromate TS
❖ It forms a red precipitate of silver
(methods) chromate which is seen against the
background of white silver
➢ In acidimetry & alkalimetry, a class of rxns chloride.
was considered that are of value in ❖ K2CrO4 + AgNO3 + NaCl → Ag2CrO4
quantitative analysis (red) + AgCl + NaNO3
o Because very slightly ionized 3. Adsorption indicators
substances or gases or both are ❖ Dichlorofluorescein (DCF) TS
formed. ❖ Eosin Y TS
➢ In volumetric precipitimetry, a class of rxns ❖ Tetrabromophenolphthalein ethyl
is dealt with that require the formation of ester (TEE) TS
relatively insoluble substances or ❖ These indicators are used in the
precipitates to cause the rxns to go to analyses of halides by direct
sufficient completion to be quantitative in titration with silver nitrate solution
nature. ❖ They are weak organic acids
➢ The solubility product principle may be ❖ End point:
applied to all precipitation rxns. o Color of the silver halide
precipitate changes
Determination of the End Point abruptly
➢ Cessation of precipitation or the ▪ Because the
appearance of a turbidity adsorbed indicator
➢ Use of internal indicators anions
➢ Instrumental methods,
o i.e., potentiometric of a turbidity
Silver Nitrate (AgNO3)
➢ Solvent
Indicators o Diluted HCl
1. Ferric ammonium sulfate TS ➢ Notes:
❖ In direct and residual titrations o No need to standardize against a
employing std ammonium primary standard since AgNO3 is a
thiocyanate solution substance of high purity.
o SCN + Ag or Hg2+ → AgSCN o Protect the silver chloride from
or Hg(SCN)2 (white) Light as much as possible during
o The thiocyanate reacts with the determination of the normality
the silver or mercuric ions of the AgNO3 solution.
present to form a white o Allow to stand in the dark to
precipitate of silver or minimize the reduction of silver
mercuric thiocyanate chloride → free silver is produced.
❖ As soon as all the silver or mercury o The purplish color of the
has been precipitated precipitate when exposed to light
o SCN + FeNH4(SO4)2 → is due to the free metal formed in
Fe(SCN)3 (red) the precipitate.
o the thiocyanate ion reacts
with ferric ammonium 𝒘𝒕. 𝒐𝒇 𝑨𝒈𝑪𝒍 𝒙 𝑨𝒈𝑵𝑶𝟑 /𝑨𝒈𝑪𝒍
sulfate to form red ferric 𝑵=
𝟒𝟎𝒎𝑳 𝒙 𝟎. 𝟏𝟔𝟗𝟖𝟕
thiocyanate
NORIENE MAIQUEZ 28
➢ AgNO3 = 169.87g/mol/1000 = 0.16987 form red ferric thiocyanate, marking the

➢ AgCl = 143.32g/mol end-point of titration:
FeNH4(SO4)2 + 3NH4SCN → Fe(SCN)3 + 2(NH4)2SO4
Ammonium Thiocyanate
(NH4SCN) ➢ The solution must be acidified with HNO
➢ Solvent 3 to prevent the hydrolysis that ferric salts
o H2O (Water) undergo in neutral solution.
➢ Secondary Std. ➢ Chlorides must be absent, since the
o 0.1N Silver Nitrate (AgNO3) chlorides of Ag and Hg are more soluble
➢ Indicator than the respective SCN–.
o Ferric Ammonium Sulfate TS Assay of Phenylmercuric
(FeNH4(SO4)2)
➢ Endpoint Nitrate for Mercury Content
o Red-brown color ➢ Solvent
➢ NH4SCN is deliquescent → a slight excess is o H2O
used during preparation. ➢ CH3COOH + Zn dust → reduces the Hg2+
➢ KSCN may be used if desired. ion to free elemental mercury → forms an
Amalgamates with the excess Zn metal →
dissolved in dilute HNO3 (1 in 2)
AgNO3 + NH2SCN → AgSCN↓ + NH4NO3
➢ CH4N2O + KMnO4 → permanent ______
White color → decolorized with _______
FeNH4(SO4)2 + 3NH4SCN → Fe(SCN)3 +2(NH4)2SO4 ➢ Indicator
o Ferric Ammonium Sulfate
➢ Oxides of nitrogen give colored salts with (FeNH4(SO4)2)
ferric alum. ➢ Titrant
➢ Solutions containing oxides of nitrogen o NH4SCN
and ➢ Endpoint
the HNO3 used in the preparation and o Red due to the formation of
standardization should be boiled prior to Fe(SCN)3
the ➢ Hg2+ ion does not yield a copious
addition of the indicator precipitate upon titration with NH4SCN as
does Ag+.
➢ The presence of halide ions (Cl, Br and I)
N1V1 = N2V2 will
interfere with the determination of Hg 2+
➢ HgCl2 > HgBr2 > Hg(SCN)2 > HgI2 >
Topic 2: direct titration Hg(CN)2
Assay of Sodium Lauryl Sulfate

(method) for Sodium Chloride Content
➢ Compounds of Ag and Hg that can be ➢ Solvent
readily converted into soluble Ag or Hg2+ o H2O
salts may be estimated by direct titration ➢ Neutralize with dilute HNO3
with standard NH4SCN solution using ➢ Indicator
FeNH4(SO4)2 as indicator. o Potassium Chromate (K2CrO4)
➢ Chemical rxns involved: Assay of Iopanoic Acid Tablets
AgNO3 + NH4SCN → AgSCN↓ + NH4NO3
➢ Chemical name of iopanoic acid
o 3-amino-α-ethyl-2,4,6-
Hg(NO3)2 + 2NH4SCN → Hg(SCN)2 + 2NH4NO3
triiodobenzenepropionic acid
➢ Solvent
➢ When all the metallic ion has been
o NaOH (1 in 20)
precipitated as thiocyanate, the NH4SCN
reacts with the ferric alum indicator to
NORIENE MAIQUEZ 29
➢ React with powdered Zn + CH3CH2COOH o Bomides

(propionic acid) o Iodides
➢ Titrant o Cyanides
o AgNO3 o Thiocyanates
➢ Indicator o Sulfides
o TEE (Tetrabromophenolphthalein o Phosphates
ethyl ester) o Arsenates
o Carbonates, etc.
➢ End-point
o Yellow → green
Assay of Sodium Chloride
➢ Solvent
Assay of o H2O + AgNO3
Benzyltrimethylammonium ➢ HNO3 is added to prevent the precipitation
of Ag as CO3-, PO43-, and to prevent
Chloride hydrolysis of the ferric alum.
➢ Titrant ➢ C6H5NO2 forms a film over the precipitated
o AgNO3 AgCl particles to prevent reaction with
➢ Indicator NH4SCN.
o DCF (Dichlorofluorescein) TS ➢ Titrant
➢ Notes: o NH4SCN
o DCF is a weak organic acid whose ➢ Indicator
ionization is dependent on the pH o FeNH4(SO4)2
of the titrated solution.
o pH < 4 → faint endpoint
(𝒎𝒍𝑨𝒈 𝒙 𝑵) − (𝒎𝒍𝑺𝑪𝑵 𝒙 𝑵) 𝒙 𝟎. 𝟎𝟓𝟖𝟒𝟒 𝒙 𝟏𝟎𝟎
o Azacyclonol (1 in 200) → pH 5-7 % 𝑵𝒂𝑪𝒍 =
o Keeps AgCl in a colloidal state → 𝑺𝒂𝒎𝒑𝒍𝒆 𝒘𝒕 (𝒈)
sharper color change
Topic 3: Residual titration Topic 4: Sodium tetraphenyl
(Volhard method) boron (titration)

➢ This method is based on the complete ➢ Na(C6H5)4B quantitatively precipitate:
precipitation of insoluble silver salts from 1. Organic nitrogen
nitric acid solution by the addition of ▪ Alkaloids
excess standard silver nitrate solution to a ▪ Amines
soluble salt ▪ Quaternary salt
➢ The determination of the amount of silver 2. Ammonium
nitrate solution in excess by residual 3. Potassium
titration with standard ammonium 4. Silver ion
thiocyanate solution, using ferric
ammonium sulfate as the indicator R4NCl + Na(C6H5)4B → R4N(C6H5)4B↓ + NaCl
➢ Excess AgNO3 solution
➢ Titrant NH4+ +Na(C6H5)4B → NH4(C6H5)4B↓ + Na+
o NH4SCH
➢ Indicator ➢ Quaternary cmpds will react with certain
o FeNH4(SO4)2 dyes such as bromophenol blue
Purity of a Soluble Chloride R4N+Cl- + Ind → R4N-Ind + Cl-

➢ This may be determined thru residual Blue chloroform-colored complex
titration provided that other substances
which form precipitates with AgNO3 are ➢ The colored complex reacts with sodium
absent. tetraphenyl boron to form an insoluble
➢ Substances other than chlorides that cmpds with the liberation of indicator
produce slightly soluble silver salts are:
NORIENE MAIQUEZ 30
R4N-Ind + Na(C6H5)4B → R4N(C6H5)4B + Na+ + Ind o Oxalate-permanganate – oxidizing

Colorless agent
➢ With the introduction of the analytical
➢ The titration uses chloroform as an reagent disodium ethylenediamine
extraction indicator in the same way it is tetraacetate, commonly referred to as
used in the determination of the iodides EDTA
with potassium iodate where the titration o A new volumetric procedure
ceases when the chloroform has lost all involved for metal determination
the iodine color. employing metal-ion indicator in
➢ In the determination of benzathonium the same manner that pH
chloride or cetylpyridinium chloride indicators are used in acid—base
o The sample is dissolved in water, to titration.
which is then added to indicator Complexation Reaction
solution, chloroform and the entire
mixture is slightly alkalinized before ➢ Based on the formation of a coordination
titration with the sodium complex.
tetraphenylboron ➢ Most, if not all, metals form coordination
➢ END POINT complexes with anions or molecules.
o When chloroform layer turns ➢ Anions/molecules that react with metal
colorless as the nitrogen cmpd is ions must donate an unshared pair of
released from the dye complex to electrons to form a coordinate covalent
precipitate with the (ex. N in Ammonia) bond
tetraphenylboron. o They are called ligands
o Covalent bond – electron shared
To Prepare and Standardized between two atoms
Sodium Tetraphenylboron o Coordinate – 2 electrons shared by
1 atom
➢ Dissolve an amount of Sodium
➢ Example:
Tetraphenylboron equivalent to 6.846 in
o Metal ion + anion
dist. H2O to make 1L. this will give a
▪ Fe+2 + 6CN → Fe(CN)6-4
concentration of 0.02M solution.
▪ Ferro Cyanide
➢ The solution is standardized by gravimetric
▪ Complex ion
method using KHP solution as precipitant
➢ Anionic Ligands
Topic 5: complexation o X-
o CN-
(methods)
o SCN-
o OH-
o RCOO-
➢ Historically, the quantitative analysis of
o S-2
inorganic pharmaceuticals containing
o C2O4-2, etc.
metal ions such as:
➢ Example:
o Al
o Metal ion + molecule
o Bi
▪ Cu+2 + 4NH3 → Cu(NH3)4+2
o Ca
▪ Tetraamine Copper 2
o Mg
▪ Complex ion
o Zn
➢ Molecular ligands
o Was performed using Gravimetric
o H2O
Methods which involved:
o NH3
▪ Precipitation
o RNH2
▪ Filtration
o Pyridine
▪ Washing
o Ethylenediamine, etc.
▪ Drying or Ignition to
➢ Ligands that have (or share) only one
constant weight
electron pair, are called unidentate
➢ Official calcium preparation were later
o “Dentate” = a tooth-like projection
analyzed volumetrically using an oxalate-
➢ Unidentate
permanganate method.
NORIENE MAIQUEZ 31
o Ammonia o CuY-2 = 18.8

➢ Bidentate o HgY-2 = 21.8
o Glycine complexed with Cu+2 o MgY-2 = 8.7
o Ethylenediamine complexed with o ZnY-2 = 16.5
Zn+2 ➢ For successful titration with EDTA, the
➢ Multidentate: stability constants of the complex formed
o EDTA (most commonly used ligand must be greater than 8.
in volumetric analysis ➢ Li and Na (both monovalent) form very
o EDTA – very ideal weak complexes and cannot be titrated.
➢ Hexadentate ➢ Ag and Ba stability constant are just below
o Most stable complex 8.
➢ Metal-ion + EDTA → complex ➢ Fe+3 (color brown) and Cu+2 (color blue in
➢ EDTA will react with metal ions to form a H2O) yield highly colored complexes
water-soluble, stable complex, or chelate cannot easily be titrated visually.
compound. ➢ Nickel and chromium = GREEN
Complex Chelate
𝑴𝑾
A metal ion that The combining (M1V1 − M2V2)( )
𝟏𝟎𝟎𝟎
combines with a molecule contains two
molecule which or more groups that
donate electrons donate electron. ➢ Anions which can form insoluble
➢ The reaction is rapid and quantitative with precipitates with certain metal ions can be
such polyvalent metal ions assayed indirectly by determining the
o Al+3 amount of metal liberated form the
o Bi+3 precipitate or by determining the amount
o Ca+2 of metal by back titration of the excess
o Cu+2 metal ion after treatment of an anion with
o Hg+2 a fixed amount.
o Mg+2 Factors Influencing EDTA
o Zn+2
➢ Monovalent metal ions yield relatively
Reaction
weak or unstable complexes. ➢ Activity of metal ion
➢ Dissociation of EDTA is pH dependent ➢ pH at which titration is run
➢ In all EDTA complexation reactions the ➢ presence of interfering ions such as:
ratio of the EDTA to the metal ion is 1:1 o cyanide (kalaban ng EDTA)
➢ The five membered rings formed in the M- o citrate
EDTA complex are strain-free and are the o tartrate, etc.
most stable. o and other complex forming agents
o Organic molecule – most stable o the higher the stability constant,
ring the more acid the pH at which
➢ In complexometric reaction, the formation complexation is run
of a stable, soluble complex is the driving ▪ ↑Ks ↑pH
force in the reaction o organic solvent ↑ stability of
o The application of the law of mass complex while neutral salts such as
action to the reaction equilibrium is NaCl ↓ the stability
termed the STABILITY CONSTANT ▪ ↑Stability ↓pH
Masking
[𝑪𝒂𝒀−𝟐 ]
𝑲𝒔 = = 𝟐. 𝟓 𝒙 𝟏𝟎𝟏𝟏 ➢ pH adjustment could react also as
[𝑪𝒂+𝟐 ] 𝒙 [𝒀−𝟒 ] masking
➢ Determination of a metal in the presence
Stability Constants of Metals of another metal
➢ Masking agents itself is a cmpd capable
Determined by EDTA Titration of entering a complexation reaction
o AlY- = 16.1 (Auxiliary complexing agents)
o BlY- = 8.6 ➢ Ex.
o CaY-2 = 10.7
NORIENE MAIQUEZ 32
1. Triethanolamine ➢ Eriochrome black T (an azo dye, best used

▪ Mask Al-EDTA, to with Mg+2 and Zn+2 titration) x’ss EDTA
accomplish Mg-EDTA causes a red to blue color change at near
complexation neutral pH. Its solution decomposes easily.
2. Thioglycols ➢ Calmagite/Calgamite
▪ Masking agents for metal o Structurally similar to E black T but
(Hg and Cu) which react more stable. Its color change is
with -SH group. similar to E black T.
3. KCN ➢ Diphenyl Carbazone → forms a purple
▪ Can mask Co, Ni, Cu, Zn complex with Hg
4. NH4F o Ex. Ca-Ind + Hg+2 → Hg-Ind + Ca+2
▪ Mask Ca, Mg, Al, and allow ➢ Hydroxynaphthol blue → blue end point
titration of Zn upon liberation
5. Other Masking Agents o Kapag complex no coloe
▪ Ascorbate o Best for calcium preparation
▪ Citrate ➢ Pyridylazonaphthol → violet CuHInd at pH
▪ Tartrate (good masking for 5 to 5.5
Sb) ➢ Dithizone (Ins in water, alcohol as solvent)
➢ Masking can also be accomplished by → rose pink color with Zn
adjusting the pH of the titration medium o Ex. Assay of Bi content of
➢ Ex. Bi will form complex with EDTA at pH 2 Glycobiarsol)
in the presence of most other metals ➢ Bi – EDTA + 0.025M ZnSO4
without interference with them 0.05M back titrated
➢ Ex. Zn will not interfere with Ca titration at a
pH 13.
𝑔 372.24
M x V = 𝑔𝑚𝑓𝑤 = g = (0.05M) (500mL) ( 1000 )
Reagent
= 9.306g (500mL)
➢ Disodium salt is preferred over the free
acid in preparing the std solution of EDTA 18.6 (1L)
o Much more soluble – H2O soluble
o Nonhygroscopic Std. – CaCO3
o Very stable
Ind. – Hydroxylnaphthol Blue
➢ C10H14N2Na2O8∙2H2O (372.24)
o Use water free metal (glass E. Point – Blue
distilled)
o Stored in polyethylene or glass 𝑊 𝑖𝑛 𝑚𝑔
M=
container boiled in an alkaline 2% (100.09)(𝑉)
EDTA – to remove metal ions.
Colorimetric Indicators M=
𝑔
(𝑣)(𝑔𝑚𝑓𝑤)
M=
𝑔
(𝑣)(0.10009)
(Metallochromic Indicators)
➢ Qualities: M=
𝑤 𝑖𝑛 𝑚𝑔 1𝑔
x
1000𝑚𝑔
x
1000𝑚𝐿
o Sharpness of color change at the (100.09)(𝑣) 1,000,000𝑚𝐿 1𝑔 1𝐿
end point
o Specificity 𝑚𝑔
Ppm =
o Stability constant smaller than M- 𝐿
EDTA
▪ i.e., the indicator must give Gmfw = gram milli formula wt.
up the metal to titrant EDTA
M-Ind + EDTA → M-EDTA + Ind.
➢ Can form complex with metal ions.
(Complex and uncomplex form have
different colors)
NORIENE MAIQUEZ 33
Chapter 8
Oxidation-Reduction Methods
➢ The chemical reactions that occur in Fe+2 → Fe+3 + e
neutralization and precipitation methods of 2I- → I2 + 2e
analysis take place w/out change in
valence. GêROa
➢ Oxidation-Reduction methods of analysis ➢ Gain electrons is oxidizing agent and
involve a change in valence of the reacting undergo reduction.
substances. o G = Gain
o ê = electrons
Theory o R = reduction
➢ Direct combination of elements – simplest o Oa = Oxidizing agent
type of oxidation-reduction Ce+4 + e → Ce+3
o Oxygen gas unites with hydrogen
Fe+3 + e → Fe+2
gas, forming water
O2 + 2H2 → 2H2O Standard Solutions
o The oxygen is reduced and the OXIDIZING AGENT REDUCING AGENT
hydrogen oxidized. • Ferric ammonium • Ferrous ammonium
o Carbon burns in the presence of sulfate sulfate
oxygen to form carbon dioxide • Potassium • Oxalic acid
permanganate • Potassium arsenite
C + O2 → CO2 • Potassium dichromate • Titanium chloride
o Carbon oxidized and oxygen is • Potassium bromate • Sodium thiosulfate
reduced • Potassium iodate
• Potassium ferricyanide
o Carbon unites with sulfur to form
• Ceric sulfate
carbon disulfide • Iodine
C +2S → CS2 • Bromine
➢ The number of electrons gained by a given
o The carbon is oxidized and the sulfur
oxidizing agent sometimes depends on the
reduced.
conditions
➢ When one substance is oxidized, some other
o E.g., pH under w/c the reaction is
substance must be correspondingly
carried out
reduced
o Permanganate ion → Manganous
➢ When one substance is reduced, some
ion
other substance must be correspondingly
▪ Since each molecule of
oxidized.
KMnO4 gains five electrons
➢ Oxidation-reduction that takes place in the
when permanganate is
official assay process are between
reduced in acid media.
electrolyte in aqueous solution.
o Dichromate ion → Chromous ion
FARADAY’S LAW: o Bromate ion → Bromide ion
➢ A change in charge of one equivalent to o Ceric ion → Cerous ion
the gain or loss of 96,500 C of electricity for o Iodine → Iodide ion
each formula weight of element or group of ▪ The reduction of the iodine in
elements involved. potassium iodate to lower
oxidation states varies
LêORa considerably, depending on
➢ Reactant which loses electrons is the conditions specified for the
reducing agent and undergo oxidation various assays.
o L = Loses ➢ Std. solutions of potassium iodate are usually
o ê = electrons expressed in terms of molarity rather than
o O = Oxidation normality.
o Ra = Reducing agent
NORIENE MAIQUEZ 34
➢ Reducing agents used for the preparation ➢ Indicator: KMnO4

of std solutions are oxidized. ➢ End point: Pale pink
o Oxalate ion → Carbon dioxide 𝒈
Titer NxV=
o Thiosulfate ion → Tetrathionate ion 𝒈𝒎𝑬𝑾
o Arsenite ion → Arsenate ion gmEW =
0.001701𝑔
= 0.01701 or 0.017g/me
(0.1𝑁)(1𝑚𝐿)
o Titanous ion → Titanic ion
o Ferrous ion → Ferric ion ➢ Note:
o Hydrogen peroxide generally acts as
Topic 1: permanganate an oxidizing agent and is reduced to
H2O – reduces the potassium
(methods)
permanganate while it is being
oxidized to oxygen, O2.
➢ KMnO4 can be standardized easily Assay of Malic Acid in Cherry Juice

➢ Rxn of permanganate in solution are rapid. Solution (Indirect Titration)
➢ It also serves as an indicator in titrations ➢ Employed with those cmpds that can be
o Very slight excess of permanganate converted through chemical reactions to an
imparts to solutions as a distinct pink equivalent amount of oxalate, which in turn
color. can then be quantitatively oxidized by
Preparation and Standardization of permanganate.
Potassium Permanganate ➢ The malic acid is converted to an
equivalent amount of calcium salt, which is
➢ Solvent: H2O converted to insoluble calcium oxalate
➢ Analyte/Std. Soln.: Sodium Oxalate o The oxalate is then liberated and
o Gmew: 0.067 oxidized with permanganate.
➢ Titrant: KMnO4 ➢ Analyte: Cherry Juice
➢ Indicator: KMnO4 ➢ Titrant: KMnO4
➢ End Point: Pale Pink ➢ Indicator: KMnO4
➢ Notes: ➢ T.S.: Ammonium Oxalate
o Any organic matter that may be ➢ Notes:
present in distilled water is o The malic acid reacts with calcium
decomposed by potassium carbonate → forming the soluble
permanganate. calcium malate
o Through asbestos to remove all o By treatment of the calcium malate
traces of manganese dioxide → acts with the ammonium oxalate
as a catalyst ▪ Equivalent amount of
o Sodium oxalate is the best std. to use reasonably pure calcium
in the standardization of potassium oxalate
permanganate – very pure o Ammonia TS is used to alkalinize the
condition soln. and keep the calcium oxalate
o When permanganate solutions are insol.
diluted to an exact normality, H2O o The calcium oxalate crystals form
freshly distilled from permanganate slowly and grow sufficiently large so
soln. should be used to avoid the that filtration is readily accomplished
introduction of organic matter. after the brief heating period.
o Soln. of oxidizing agents should o The calcium oxalate, equivalent to
never be titrated from Mohr burets the calcium malate, which in turn is
▪ Since the oxidizing gent equivalent to the malic acid
attacks the tubber and the o The same oxidation-reduction
KMnO4 titer decreases. reactions occur in the determination
Assay of Hydrogen Peroxide Solution of dibasic calcium phosphate.
o The pH during this analysis must be
(Direct Titration) carefully controlled to minimize the
➢ Analyte: H2O2 coprecipitation effects of sodium,
➢ Titrant: KMnO4 potassium, and magnesium oxalates
NORIENE MAIQUEZ 35
Residual Titration Methods ➢ Indicator: KMnO4

➢ T.S.: Ferric Ammonium Sulfate TS
➢ Titration in which an excess of std potassium ➢ End Point: Pale pink
permanganate soln. is employed to oxidize ➢ NOTES:
a substance, and the amount in excess is o Titanium dioxide is soluble in hot
determined by reduction sulfuric acid
o Excess std oxalic acid ▪ The silicic acid is insoluble
o Or excess ferrous ammonium sulfate and is filtered off.
and back titration with more std o When the color of the potassium
potassium permanganate permanganate persists, it means
➢ Titration in which an excess of standard that there are no reducing
oxalic soln. is added to the substance and substances left in the column.
the excess oxalic acid is titrated with std.
potassium permanganate.
𝒎𝒍 𝒙 𝑵 𝒙 𝒎𝒆𝒒 𝒘𝒕 𝒙 𝟏𝟎𝟎
Assay of Manganese Dioxide, 𝒔𝒂𝒎𝒑𝒍𝒆 𝒘𝒕.
= % 𝑻𝒊𝑶𝟐
Precipitated
➢ Solvent: H2O
➢ Titrant: Potassium Permanganate Preparation and Standardization of
0.1N Oxalic Acid
MnO2 + H2O2 + H2SO4 → MnSO4 + 2H2O + O2↑ ➢ Analyte: Oxalic Acid
o GmEW =
➢ Solvent: H2O
➢ NOTES: ➢ Titrant: KMnO4
o The hydrogen peroxide is added in ➢ Indicator: KMnO4
measured excess, and the residual ➢ End Point: Pale Pink
peroxide is determined by titration ➢ NOTES:
with standard KMnO4. o Purest oxalic acid obtained varies in
o A blank is run under the same composition
conditions to correct for any ▪ Because of differences in its
reactions of the peroxide such as moisture content
decomposition. o Acid is heated sufficiently to drive off
absorbed moisture, it tends to lose
(𝐦𝐥𝐛𝐥𝐚𝐧𝐤 − 𝐦𝐥𝐚𝐬𝐬𝐚𝐲 ) 𝐱 𝐍 𝐱 (𝟖𝟔. 𝟗𝟒/𝟐𝟎𝟎𝟎) 𝐱 𝟏𝟎𝟎 water of crystallization
= % 𝐌𝐧𝐎𝟐
𝐬𝐚𝐦𝐩𝐥𝐞 𝐰𝐭. o Error is minimized by standardizing
the oxalic acid soln. against the
same permanganate solution with
o This is an example of how an
w/c it is to be used in analyses.
oxidizing substance (MnO2) can be
o Normality of an Oxalic acid soln.
determined indirectly with another
determined by titration with std alkali
oxidizing agent, KMnO4, by
(NaOH)
measuring the amount of unreacted
▪ Indicator: Phenolphthalein TS
hydrogen peroxide in the sample as
▪ Titrate with 0.1N oxalic acid
compared with that found in the
▪ Until pink color disappears
blank.
▪ Brought to gentle boil to
o The difference, as measured by the
expel all CO2
volumes of potassium
permanganate, represents the Assay of Sodium Nitrite
equivalent amount of MnO2 in the ➢ Analyte: Sodium Nitrite (NaNO2)
sample. o GmEW = 3.450mg/1000 = 0.0345
Assay of Titanium Dioxide ➢ Solvent: H2O
➢ Titrant: KMnO4
➢ Analyte: Titanium Dioxide
➢ Indicator: KMnO4
o GmEW = 7.990mg/100 = 0.0799
➢ End Point: Pale Pink
➢ Solvent: H2SO4
➢ Titrant: KMnO4
NORIENE MAIQUEZ 36
➢ NOTES: Orthophenanthroline Test Solution

o Sodium nitrite is deliquescent and is
➢ The ferrous sulfate solution must be
therefore directed to be dried in a
prepared immediately before dissolving the
desiccator over sulfuric acid
orthophenanthroline
previous to weighing.
➢ The base orthophenanthroline dissolves
o Nitrous acid is oxidized by the
readily in aqueous solns. of ferrous sulfate, 3
permanganate to nitric acid
molecules combining with one ferrous ion to
o If sodium nitrite will be acidified with
form complex ions, known as ferroin, w/c
sulfuric acid, nitrous acid w/c is
have an intensely red color.
volatile, would be lost.
➢ Strong oxidizing agents convert the ferrous
o Oxidation of nitrous to nitric acid
to a ferric complex → blue color.
proceeds slowly at ordinary
temperature
▪ However, rapid at 40°C C12H8N2 + Fe+2 → Fe(C12H8N2)3+2 ↔ Fe(C12H8N2)3+3 + e
o X’ss permanganate is reduced by Orthophenanthroline Ferrous complex Ferric complex
adding an x’ss of std oxalic acid and (colorless) (red) (blue)
titrating the x’ss oxalic acid with ➢ The color change, red to blue, is reversed
more of the std permanganate to by reducing agents
appearance of the permanganate ➢ The blue oxidized form is stable
color (pale/light pink). Preparation & Standardization of
Topic 2: ceric sulfate titration 0.1N Ceric Sulfate
(Cerimetry)
(methods) ➢ Analyte: Arsenic Trioxide
o gmEW = 4.946MG/100 =
➢ Ceric sulfate in diluted sulfuric acid is a 0.04946g/me
strong oxidizing agent and considerably ➢ Titrant: Ceric Sulfate
more stable than std permanganate soln. ➢ Indicator: Orthophenanthroline TS
➢ Sufficient sulfuric acid is present to prevent ➢ End Point: pink color to very pale blue
hydrolysis and precipitation of basic salts ➢ NOTES:
➢ Permanganate can be reduced to any of o The trace of osmium tetroxide is
several oxidation states added to catalyze the otherwise
o Ce+3 always results on reduction of slow reaction between ceric ion and
Ce+4 the arsenite ion.
➢ Ceric sulfate combines many of the
advantages of permanganate and
dichromate
1. The solutions are stable even on boiling
2. They react quantitatively with oxalate or
arsenite ion, and either sodium oxalate 𝐰𝐭 𝐨𝐟 𝐚𝐫𝐬𝐞𝐧𝐢𝐜 𝐭𝐫𝐢𝐨𝐱𝐢𝐝𝐞
or arsenic trioxide (primary std.) 𝐍=
𝐦𝐥 𝐱 𝟎. 𝟎𝟒𝟗𝟒𝟔
3. The cerous ion is colorless and does not
obscure the indicator end point
4. No intermediate products are formed in Assay of Ferrous Sulfate Tablets
the reduction of ceric cerium
5. Rather high conc. of chloride ion are not
(Cerimetry)
oxidized by ceric salts, so that ferrous ➢ Analyte: Ferrous Sulfate Tablets
iron can be determined in the presence o gmEW = 27.80/100 = 0.0278
of chlorides ➢ Solvent: Diluted H2SO4 + freshly boiled and
6. The ferrous phenanthroline ion (ferroin) is cooled H2O
a very satisfactory indicator in titration ➢ Titrant: Ceric Sulfate
with ceric salts. ➢ Indicator: Orthophenanthroline TS
▪ Phenanthroline ion (ferroin) – true ➢ End Point:
redox indicator ➢ NOTES:
NORIENE MAIQUEZ 37
o The ff. oxidation-reduction reaction

occurs between the ceric sulfate
and the ferrous sulfate
2FeSO4 + 2Ce(SO4)2 → Fe2(SO4)3 + Ce2(SO4)3
o Since the estimation of the iron salts
is based on the oxidation of the
ferrous ion to the ferric ion, the
variations in the procedures for
ferrous gluconate and ferrous
fumarate are necessary to ensure
that the iron is in the ferrous state
before oxidation with ceric sulfate.
Assay of Ascorbic Acid
(Cerimetry)
➢ Analyte: Ascorbic Acid
o gmEW =
➢ Std oxidizing agent: Dichlorophenol-
indophenol
o Standardized using USP ascorbic
acid
➢ Indicator: Not necessary
➢ Titrant: metaphosphoric acid & acetic acid
w/ dichlorophenol-indophenol
➢ End Point: Rose-pink color
➢ NOTES:
o From the ascorbic acid equivalent
of the std dichlorophenol-
indophenol soln. the ascorbic acid
content can be calculated from the
volume of titrant consumed.
o A change in color is also produced
when several other organic
substances are reduced.
Assay of Gentian Violet & Gentian
Violet Solution
(Cerimetry)
➢ Analyte: Gentian Violet & Gentian Violet
Soln.
o gmEW =
➢ Titrant: Std. Ferric Ammonium Sulfate
➢ End Point: Red
➢ NOTES:
o An x’ss of titanium trichloride in an
inert atmosphere is used, and the
x’ss is back-titrated with std. ferric
ammonium sulfate solution.
o Red color end point because of the
formation of a ferric thiocyanate
complex
NORIENE MAIQUEZ 38
Chapter 9
Oxidation-Reduction: Iodimetric and
Iodometric Methods
➢ The reversible rxn can be applied in o Arsenite
analysis of reducing agents ➢ Sx (R.A.) + I2 (O.A) → Product
o E.g., thiosulfate & arsenite ➢ Std iodine soln. used in iodimetry are soln.
o By the use of std soln. of iodine of iodine in potassium iodide soln.
o Direct procedure → Iodimetry ➢ If residual method of iodimetry is
➢ Same reversible rxn can be applied employed,
indirectly in the analysis of oxidizing o X’ss iodine may be titrated with std
agents sodium thiosulfate
o E.g., ferric and cupric salts, and ▪ E.g., the assay of sodium
“available” chlorine bisulfate
o Indirect procedure known as
Iodometry
Iodometry/Iodometric
▪ Sample of oxidizing agent is ➢ Indirect
reduced with excess ➢ Std. Thiosulfate
potassium iodide (KI) and ➢ Indicator – Starch T.S.
an equivalent amount of ➢ End point – Disappearance of blue
iodine is produced ➢ Oxidizing agents
▪ Iodine is titrated with std o Ferric
soln. of sodium thiosulfate o Cupric salts
➢ Iodine is not very soluble in water but ➢ FeCl3 (O.A.) + KI (R.A.) → I2 (O.A.) + S2O4-2
dissolves readily in the presence of (R.A.)
potassium iodide o FeCl3 – as analyte
o Formation of the triiodide ion I2 + I- o S2O4-2 – as titrant
→ I-3 ➢ Iodometric methods include some of the
➢ Alkaline solns, reaction of iodine with OH- most accurate procedures in titrimetric
produces 1st hypoiodite and finally iodate analysis
ions o Under proper conditions, the
I2 + OH- → HI + IO- presence of 1 part of iodine in
several million parts of soln is
3IO- → IO3- + 2I-
readily detected by the use of
➢ These ions oxidize thiosulfate at least starch indicator soln.
partially to a higher oxidation state ➢ Some procedures:
o E.g., sulfate and the stoichiometry o Iodine color may be used in
indicated above no longer holds observing the E.P. of a titration,
true especially a small volume of
➢ Iodine quantitatively oxidizes certain other carbon tetrachloride or carbon
reducing agents, and std soln. of iodine disulfide (iodine is soluble)
may be used in their direct titrimetric ➢ Chemical Reaction (C.R.)
analysis
I2 + 2Na2S2O3 → 1NaI + Na2S4O6
o E.g., arsenious acid
Sodium Sodium
Iodimetry/Iodimetric Thiosulfate Tetrathionate
➢ Direct ➢ X’ss potassium iodide is used as a

➢ Std Iodine reducing agent in iodometry
➢ Indicator – Starch T.S. o Iodine formed will remain in soln.
➢ End Point – Blue through interaction w/ potassium
➢ Reducing agents iodide.
o Thiosulfate
NORIENE MAIQUEZ 39
➢ Iodometric procedures are never carried o 0.1N Sodium thiosulfate

out in strongly basic solns. o 0.1N potassium arsenite
➢ Iodometric analysis of oxidizing agents →
produces equivalent amount of iodine Topic 2: direct titration with
o Sx of oxidizing agent oxidizes
iodine, sodium thiosulfate and

potassium iodide in the presence
of an acid
▪ E.g., assay of cupric sulfate
potassium arsenite
Topic 1: preparation of starch
Preparation & Standardization
(indicator solution) of 0.1N Iodine Solution
➢ Triturate 1 g of arrowroot starch w/ 10mL (Iodimetry)
cold water ➢ Analyte: NaHCO3
➢ Heat about 200mL water to boiling + o gmEW: 0.04946
starch paste with constant stirring ➢ Titrant: Iodine Solution
➢ NOTES: ➢ Standardized by: Arsenic Trioxide
o Solution of starch deteriorates ➢ Indicator: Starch T.S
rapidly, it should be prepared ➢ E.P.: Blue
freshly each day ➢ NOTES:
o β-amylose – Soluble starch o Arsenic trioxide dissolve in 0.1N
o α-amylose (amylopectin) – sodium hydroxide, dilute with water
Insoluble starch + 2 gtts of methyl orange TS and
o interaction of iodine and iodide ion diluted hydrochloric acid until
w/ the colloidal β-amylose → yellow color changed to pink.
production of an intensely blue- o Arsenic trioxide is slowly soluble in
colored soln. cold water
▪ this color change is ▪ More rapidly soluble in
reversible boiling water
▪ color being discharged ▪ Readily soluble in sodium
when the iodine is reduced hydroxide soln.
w/ sodium thiosulfate or o If iodine + to alkaline soln. → form
another reducing agent sodium hypoiodite (NaIO) – which
o sensitivity of the indicator is greater do not react readily with arsenious
in slightly acid media and is ion.
markedly decreased by o The x’ss sodium hydroxide is
temperatures above 25°C therefore neutralized with
▪ Strong solutions of hydrochloric acid using methyl
electrolytes orange as the indicator.
▪ Alcohol o Sodium bicarbonate is added to
▪ Other organic solvents neutralize the hydriodic acid, HI,
o Reversibility of color formation is formed in the reversible reaction.
decreased when iodine conc. is ▪ The NaHCO3 removes the
high. HI as rapidly as it is formed,
▪ Indicator should not be causing the rxn to go to
added in residual completion toward the
iodimetric procedures or in right
iodometric procedures • NaHCO3 acts as
▪ Results change from a buffer to keep soln.
brown to a straw-colored neutral.
solution. Na3AsO3 + I2 + 2NaHCO3 → Na3AsO4 + 2NaI +
➢ Standard Solutions 2CO2↑ + H2O
o 0.1N Iodine
NORIENE MAIQUEZ 40
o Sodium bicarbonate does not ▪ X’ss oxidizing agent and

react with iodine the arsenic are reduced w/
➢ Chemical Reactions starch or potassium iodide
As2O3 + 6NaOH → 2Na3AsO3 + 2H2O ▪ Iodine formed from the
potassium iodide is
reduced with sodium
2NaOH + I2 → NaIO + NaI + H2O thiosulfate
➢ FORMULA: ▪ pH adjusted
▪ Sodium bicarbonate is
𝐰𝐭 𝐨𝐟 𝐀𝐬𝟐 𝐎𝟑 𝐬𝐚𝐦𝐩𝐥𝐞 added, and the trivalent
𝐍= arsenic is titrated with the
𝐦𝐋 𝐨𝐟 𝐢𝐨𝐝𝐢𝐧𝐞 𝐱 𝟎. 𝟎𝟒𝟗𝟒𝟔
iodine solution
o Potassium sodium tartrate is used in
Assay of Antimony Potassium the glycobiarsol assay for arsenic
to complex the bismuth, w/c might
Tartrate (Iodimetry) otherwise interfere w/ the analysis.
➢ Analyte: Antimony Potassium Tartrate o Sulfur dioxide is converted to
(Tartar Emetic) sodium sulfite by treatment with a
o gmEW: 0.167 sodium hydroxide soln. and the
o Anthelminthics sulfite ion is oxidized to sulfate with
▪ Uses: Tx for Schistosomiasis iodine.
➢ Titrant: Iodine Soln. o The sulfur in dimercaprol and
➢ Indicator: Starch T.S. reagent sodium thioglycolate is
➢ E.P.: Blue oxidized with iodine
➢ NOTES: o The sulfhydryl group is oxidized to
o The sodium bicarbonate is added disulfide in a rxn such as
to neutralize the HI formed in the 2RSH + I2 → R−S−S−R + 2HI
rxn in a manner analogous to the
arsenious ion with iodine so that Preparation & Standardization
the reaction may proceed to of 0.1N Sodium Thiosulfate
completion quantitatively.
(Iodometry)
Notes: ➢ Analyte: Potassium Dichromate
➢ Ascorbic acid o gmEW: 0.04903
o Fairly strong reducing agent ➢ Titrant: Na Thiosulfate
o Determined by simple titration with ➢ Indicator: Starch TS
iodine solution, w/c oxidizes the ➢ E.P.: Yellow
ascorbic acid to dehydroascorbic ➢ NOTES:
acid o The Na thiosulfate is dissolved in
I2 + C6H8O6 → 2HI + C6H6O6 H2O
Oxidize ascorbic â → dehydroascorbic â ▪ Since deterioration of the
soln. results mainly from the
➢ Organic Arsenical
action of bacteria
o Determined as trivalent or
o Boiling also expels carbon dioxide
pentavalent arsenic
▪ Which, if present as
o In carbasone the arsenic is in its
carbonic acid → may act
trivalent form when it is digested
like acid in causing
with sulfuric acid & potassium
hydrolysis and
sulfate in the manner of a Kjeldahl
decomposition of the
digestion.
sodium thiosulfate.
o As the organic material is oxidized
➢ Chemical Reactions:
▪ The arsenic is reduced to
trivalent arsenic Na2S2O3 + 2H2CO3 → 2NaHCO3 + H2S2O3
o Digestion: H2S2O3 → H2SO3 + S↓
NORIENE MAIQUEZ 41
o The sodium carbonate is added to potassium iodide by standard

the soln. as a preservative to solns. of potassium permanganate
prevent acid-catalyzed hydrolysis or various primary std oxidizing
o The potassium dichromate oxidizes agents such as
the iodide ion in the presence of ▪ Potassium Iodate etc.
acid to an equivalent amount of
iodine.
Assay of Sodium Hypochlorite
o Iodine formed in this rxn will oxidize Solution (Iodometry)
a chemically equivalent amount of ➢ Analyte: Na Hypochlorite Soln.
sodium thiosulfate o gmEW: NaClO – 3.722/2000 =
▪ Vol. of Na Thiosulfate used 0.001861
in titration of iodine is ➢ Titrant: Na Thiosulfate
chemically equivalent to ➢ Indicator: Starch TS
the sx wt of potassium ➢ E.P.: Disappearance of blue color
dichromate ➢ NOTES:
➢ Calculations: o Hypochlorous acid formed from
𝐰𝐭 𝐨𝐟 𝐊 𝟐 𝐂𝐫𝟐 𝐎𝟕 sodium hypochlorite reacts with
𝐦𝐋 𝐱 𝐍 =
𝟎. 𝟎𝟒𝟗𝟎𝟑 𝐠/𝐦𝐞𝐪 the potassium iodide in the
presence of acetic acid to liberate
Or iodine.
o In the stoichiometry involved in the
𝐰𝐭 𝐨𝐟 𝐬𝐚𝐦𝐩𝐥𝐞 assay of halazone,
𝐍= ▪ Each Cl+ is converted to Cl-;
𝐦𝐋 𝐱 𝟎. 𝟎𝟒𝟗𝟎𝟑
as a result each mole of
halazone produces 2 mol or
o Pot. Iodide in x’ss of the amount 4 equiv of iodine and the
necessary for reduction of the equivalent weight of
K2Cr2O7 is employed so that the halazone is 67.52g or ¼
liberated iodine will be held in soln. gram-molecular weight.
as KI3. ➢ CALCULATIONS:
o Soln. is diluted before titration to
make the E.P. more readily
𝐦𝐋 𝐱 𝐍 𝐱 (𝐍𝐚𝐂𝐥𝐎/𝟐𝟎𝟎𝟎) 𝐱 𝟏𝟎𝟎
observed = %𝑁𝑎𝐶𝑙𝑂
▪ Since the mixture does not
𝐬𝐚𝐦𝐩𝐥𝐞 𝐰𝐭.
become colorless
▪ When all iodine is reduced ➢ CHEMICAL REACTIONS:
but rather changes from
deep-blue color of starch-
HOCl + 2KI + HOAc → I2 + KCl + KOAc + H2O
iodide-iodine complex to
light green Cr+3.
o The change in the titer of Na Preparation of 0.1N Potassium
thiosulfate solns. on standing results
primarily from bacterial action. Arsenite Solution
o The pH of the soln. prepared using ➢ NOTES:
sodium carbonate is unfavorable o The arsenic trioxide is neutralized
to the growth of the bacteria. by potassium hydroxide and forms
▪ Cleaned glassware and potassium arsenite
freshly boiled water should o The potassium bicarbonate is used
be used in preparation of to provide the pH of about 9 which
the soln. is necessary for accurate results
o Sodium thiosulfate soln. may also and a rapid reaction with iodine.
be standardized against pure
iodine dissolved in potassium
iodide soln or against iodine set
free from an acidified soln. of
NORIENE MAIQUEZ 42
Topic 3: residual titration of Topic 4: liberation of iodine from
excess iodine with sodium potassium iodide & titration
thiosulfate with sodium thiosulfate
Assay of Methionine ➢ Substances that are oxidizing agents

which cannot be determined by direct
➢ Analyte: Methionine titration with a std. soln. of a reducing
o gmEW: 0.07461 agent are assayed indirectly.
➢ Titrant: 0.1N Sodium Thiosulfate ➢ In this indirect method an equivalent
➢ Indicator: Starch TS amount of iodine produced by the
➢ E.P.: oxidation of the iodide ion in an acid
➢ NOTES: medium by the substance is determined
o The phosphate alkalinize the by a std. soln. of a reducing agent such as
reaction mixture sodium thiosulfate.
o Neutralizing the methionine as well
as the hydriodic acid, thus causing Assay of Selenium Sulfide
the rxn to proceed quantitatively. ➢ Analyte: Selenium Sulfide
Notes: o gmEW: 987.0 μg/
➢ Titrant: 0.05N Sodium Thiosulfate
➢ Assay of Methenamine Mandelate ➢ Indicator: Starch TS
o Involves the hydrolysis of the ➢ E.P.:
methenamine with hydrochloric ➢ NOTES:
acid, producing formaldehyde o Selenium sulfide is practically
▪ Which in turn is allowed to insoluble in water and organic
reduce an equivalent solvents but is soluble in fuming
amount of mercuric ion to nitric acid,
mercury. ▪ Which oxidizes the cmpd.
o The mercury so produced is then To selenious acid and
oxidized with std iodine soln., and sulfuric
the excess is determined by o The selenious acid formed is an
sodium thiosulfate. oxidizing agent which will liberate
➢ Potassium Xanthogenate iodine from potassium iodide
o Oxidized by iodine in the ff. o The amount of sodium thiosulfate
manner consumed by the iodine in the
titration is equivalent to the
2C2H5OC(S)SK + I2 → 2KI + [C2H5OC(S)S]2 selenium in the sample.
o A blank determination is run to
➢ Sodium Metabisulfite (Na2O∙2SO2) account for any iodine liberated
o Oxidation with iodine proceeds as from the potassium iodide by the
in the case of sodium bisulfite, reagents used in the analysis
sodium sulfite, and sulfurous acid in ▪ Which in turn would
which the sulfur in each cmpd. consume some sodium
Gives up two electrons and is thiosulfate.
oxidized from tetravalent to ➢ CHEMICAL REACTIONS:
hexavalent sulfur.
SeS2 + 16HNO3 → H2SeO3 + 2H2SO4 + 16NO2↑ +
5H2O
➢ CALCULATIONS:
NORIENE MAIQUEZ 43
𝐦𝐋 𝐱 𝐍 𝐱 (𝟕𝟖. 𝟗𝟔/𝟒𝟎𝟎𝟎) 𝐱 𝟏𝟎𝟎 o The x’ss potassium dichromate is

= %𝐒𝐞 measured iodometrically
𝐬𝐚𝐦𝐩𝐥𝐞 𝐰𝐭/𝟓
➢ Sugar alcohols such as mannitol
selectively reduce an acidified soln. of
Assay of Cupric Sulfate potassium periodate
➢ Analyte: Cupric Sulfate (CuSO4) o Mannitol and mannitol injection
o gmEW: 0.01596 are assayed by tx w/ x’ss
➢ Titrant: Na Thiosulfate potassium periodate reagent
➢ Indicator: Starch TS
➢ E.P.: C6H14O6 + 5HIO4 → 2HCHO + 4HCOOH + 5HIO3 +
➢ NOTES: H2O
o This assay is based on the rxn
between cupric sulfate and ➢ When potassium iodide is added
potassium iodide o The x’ss iodate and periodate are
▪ Which the copper is determined by measuring the
precipitated as cream- amount of liberated iodine
colored cuprous iodide and ➢ Blank determination will liberate more
one atom of iodine is iodine and consequently consume more
liberated for each cupric sodium thiosulfate.
ion present. ➢ Difference in volumes of sodium thiosulfate
➢ CHEMICAL REACTION: consumed is a measure of the mannitol in
the sample.
2Cu+2 + 4I- → 2Cu+ + 2I- + I2
HIO4 + 7HI → 4I2 + 4H2O
Notes: Topic 5: oxidation-reduction

➢ A residual type of iodometric procedure
may be used for substances which react methods with 0.1N bromine
quantitatively with such oxidizing agents
o Potassium ferricyanide ➢ In the assay of compounds such as
o Potassium dichromate o Aniline
o Potassium periodate o Phenol
➢ The same is treated with a x’ss of a std soln. o Resorcinol
of the oxidizing agent o Bromine
o And the x’ss oxidizing agent is ➢ Is employed as an oxidizing agent in place
subsequently determined of iodine
iodometrically. o Since it is reduced by the readily
➢ EXAMPLE: LEAD MONOXIDE oxidized organic substances in a
o Converted to lead acetate which reaction that proceeds
reacts with potassium dichromate quantitatively with the production
in the presence of acetic acid of water-insoluble bromine
substitution products
PbO + 2HC2H3O2 → Pb(C2H3O3)2+ H2O ▪ Tribromoaniline
▪ Tribromophenol, etc.
2Pb(C2H3O2)2 + K2Cr2O7 + H2O → 2PbCrO4↓ + ➢ Std soln. employed does not contain
2KC2H3O2 + 2HC2H3O2 bromine as such but rather an equivalent
amount of potassium bromates and x’ss
o Lead acetate reacts with potassium bromide.
potassium dichromate not by ➢ Bromine is liberated when the soln. is
reducing it acidified.
▪ But by a reaction which
goes to completion –
because of formation of the
insoluble lead chromate.
NORIENE MAIQUEZ 44
Preparation & Standardization ▪ Bec. The normality varies

depending on the nature of
of 0.1N Bromine, Koppeschaar’s the rxn.
Solution o The uniform reduction of potassium
iodate to iodide is generally not
➢ Analyte: K Bromate + K Bromide
feasible in the direct titrimetric
o gmEW:
procedure and has no application
➢ Titrant: 0.1N Sodium Thiosulfate
in official assay methods.
➢ Indicator: Starch TS
o If x’ss iodate is used, any iodide
➢ E.P.:
formed is oxidized to iodine and
➢ NOTES:
the x’ss iodate and the iodine are
o When the soln. of potassium
determined iodometrically.
bromide and potassium bromate is
o Under certain conditions, the
acidified with hydrochloric acid,
iodate and iodine formed as
▪ Bromine is set free:
reduction products of iodate and
are quantitatively converted to I+.
5KBr + KBrO3 + 5HCl → 6KCl + 3Br2 + 3H2O
▪ The iodine initially formed
by the reduction of iodate
o The liberated bromine oxidizes
undergoes solvolysis in a
iodide to an equivalent amount of
polar solvent.
iodine:
o The iodine cation forms iodine
monochloride when the HCl
2KI + Br2 → 2KBr + I2 concentration is sufficiently great
o Chloroform or carbon tetrachloride
o The flask should be tightly is added to make the end-point
stoppered after the addition of the observation possible
acid to prevent the escape of o Iodine is produced and the
bromine vapors. chloroform layer becomes
colored.
Topic 6: oxidation-reduction
Assay of Potassium Iodide
methods with potassium iodate ➢ Analyte: Potassium Iodide
o gmEW: 0.0166
➢ Titrant: 0.05M Potassium Iodate
➢ Potassium iodate my be used as oxidizing
➢ Indicator:
agent in the assay of a number of
➢ E.P.: Disappearance of purple color
substances
➢ NOTES:
o Iodides
o Several official iodides are assayed
o Arsenites
by use of Std. Potassium iodate.
o Other reducing agents
o As the E.P. in the titration is
➢ The method depends upon the formation
approached, vigorously shaking is
of iodine monochloride in strong
necessary
hydrochloric acid soln.
▪ Bec. The heterogenous
Preparation of 0.05M nature of the mxt. With
iodine and iodate is
Potassium Iodate
different phases.
➢ NOTES: ➢ CHEMICAL REACTIONS
o Potassium iodate is dried to ensure
its freedom from moisture.
2KI + KIO3 + 6HCl → ICl + 3KCl + 3H2O
▪ Since potassium iodate is a
very stable salt and can be
obtained in a very pure Notes:
condition ➢ In the assay of Benzalkonium chloride
o Std iodate soln. of known molarity using potassium iodate as the titrant,
are usually employed
NORIENE MAIQUEZ 45
o The sample is treated with an exact

volume of a potassium iodide soln. 2I- + 2HNO2 + 2H+ → I2 + 2NO↑ + 2H2O
o Chloroform-soluble benzalkonium
iodide complex is removed o This method is applicable also in
▪ The x’ss potassium iodide the assay of many other cmpds
determined with the having a primary arylamino
potassium iodate. grouping
o A blank determination is run with o The end-point is determined
water substituted for the sample. electromecally using suitable
➢ Hydralazine hydrochloride is a substituted electrodes.
hydrazine and as such is capable being o The aromatic secondary amines
oxidized by potassium iodate in the will form quantitatively a nitrosation
manner of hydrazine. cmpds
▪ whereas tertiary amines on
Preparation & Standardization rxn with nitrous acid will
of 0.1M Sodium Nitrite Solution result in ring substitution.
➢ Analyte: Sodium Nitrite o Primary aliphatic amines form an
o gmEW: 0.01722 unstable diazonium salt w/c
➢ Titrant: decomposes to form a primary
➢ Indicator: Starch Iodide Paste TS. alcohol.
➢ E.P.: blue ring when touched to starch o Secondary amines react as
iodide paper. arylamines but not usually
➢ NOTES: quantitatively.
o Since the standardization rxn and o Tertiary amines do not react with
procedure are identical with the nitrous acid.
assay method,
▪ The possibility of an end-
point error is minimized.
o It is usually desirable to conduct an
exploratory titration before the
actual titration.
o Nitrous acid, formed when sodium
nitrite soln. is introduced into the
acid rxn mxt., react with the
primary amino group of
sulfanilamide,
▪ Forming an unstable nitrite
which decomposes with
formation of a diazonium
salt.
o This product is also unstable, and if
the rxn mxt is not kept cold,
▪ It will decompose, forming
phenol products which are
capable of reacting further
w/ nitrous acid.
➢ CHEMICAL REACTIONS
NaNO2 + HCl → HNO2 + NaCL
H2NSO2C6H4NH2 + HNO2 + HCl → H2NSO2C6H4N2Cl +

2H2O
NORIENE MAIQUEZ 46
Chapter 10
Gravimetric Analysis
(Topic 1: theory) B. Solubility Product Principle
➢ Solubility product principle is an application
➢ Chemical reactions in gravimetric analysis of the law of mass action to equilibria that
take place in accordance with the generalizes the behavior of difficulty soluble
established laws and theories of chemistry salts in their saturated solutions.
o Law of mass action ➢ Precipitation occurs, prevented or solution is
o Reversible reactions affected; solubility product principle is
o Solubility product principle involved.
o Common-ion effect ➢ The product of the conc of the constituent
ions in a saturated solution of a difficulty
A. Law of Mass Action & soluble salt for any given temp is practically
Reversible Reactions a constant, each conc being raised to a
power equal to the relative number of ions
➢ Under certain conditions may be made to
supplied by one molecule of the salt upon
continue to completion
dissociating.
➢ Under other condition may attain
➢ Solubility products of some of the more
equilibrium before completion
difficulty soluble salts dealt with in
o Resulting in erroneous data
pharmaceutical analysis.
➢ Three general conditions tend to prevent
➢ Number of different kind of ions are present
reversal of reaction
in the same solution.
1. Formation of an insoluble gas
o Greatest conc any one of them can
2. Formation of a sparingly soluble solid
attain is determined by the others.
3. Formation of very slightly ionized
o No great conc of silver can be
molecules.
present in a solution in the presence
➢ According to the law of mass action, rate of
of chlorine, for the two ions unite to
reaction is PROPORTIONAL to the product of
form a precipitate of the difficulty
the molecular conc. of the reacting
soluble salt, silver chloride.
substances.
o Silver chloride is slightly soluble in
➢ Rate of a reaction depends upon the conc.
water
of every substance taking part in the
➢ The solubility product is thus seen to be an
reaction.
ultimate value attained by the ionic product
➢ Point of equilibrium will depend upon the
when equilibrium has been established
conc. of each of the components of the two
between the undissolved solid and the
opposing reactions.
difficulty soluble salt in solution.
➢ Product of the conc of any pair of ions in
KNO3 + H2SO4 ↔ KHSO4 + HNO3 solution is made to exceed in value the
solubility product; compound formed by
➢ Rate of the reaction of potassium nitrate their union; precipitation of the compound
with sulfuric acid is expressed by the will take place until the product of the ionic
equation. conc is exactly EQUAL to the solubility
➢ At definite temp. the equilibrium constant is product value.
a fixed value for any given reaction ➢ Product of the ionic conc is made LESS
irrespective of the conc of the substances THAN the solubility product value;
present. o compound formed by their union will
➢ In quantitative analysis, an x’ss of one dissolved until product of ionic conc
component is frequently added to cause is equal to the solubility product
the reaction to go as nearly to completion value.
as possible.
NORIENE MAIQUEZ 47
C. Common-Ion Effect b. Precipitation (most usual method) –

assay of halide, sulfites, etc.
➢ Equilibrium constant does not change, no c. Electrolytic decomposition on tared
matter what the conc of the reacting electrode
substances may be. o Ex. Determination of Ag, Hg, Cu
➢ Relative conc of the reacting substances in a solution of sample
may change, but there is no change in the d. Extraction with appropriate solvent and
equilibrium constant. subsequent evaporation of the latter
➢ Solution of silver nitrate is added to a e. Volatilization of the substance to be
solution of sodium chloride, the chloride ion determined.
is momentarily present in a conc such that i. Moisture
its ionic product with the silver ion exceeds ii. Water of crystallization
the solubility product of AgCl, and insoluble iii. Carbon dioxide
AgCl is precipitated: iv. Ammonium salt
f. By absorption of the gas liberated from
Ag+ + Cl- → AgCl↓ a sample
o Ex. Determination of carbon
content in an organic
➢ Equivalent amount of silver nitrate has been
compound which is oxidized to
added, and the system has acquired
CO2 and this is absorbed in
equilibrium, the conc of silver ions will be
tared potash bulb.
exactly equal to the conc of chloride ions.
➢ Measurement of the weight of a substance
➢ Supernatant liquid, which is a saturated
in a sample
solution of AgCl
➢ calculation of the weight of a substance in
➢ Small amount of a soluble silver salt or a
a sample from the weight of a chemically
soluble chloride is added
equivalent amount of some other
o Slight further precipitation will take
substance
place.
➢ The substance to be measured
➢ Conc of silver ion is increased by the
gravimetrically is separated from other
addition of a soluble silver salt.
substances composing the sample by
➢ Concentration of chloride ion must
physical methods, purified, and weighed
decrease and conversely that if the conc of
without chemical change.
chloride ion is increased by adding a
soluble chloride
➢ Conc of silver ion must decrease since their NaCl + AgNO3 → AgCl + NaNO3
product remains constant.
Topic 2: gravimetric method

➢ A chemically equivalent amount of some
product can be obtained from a reactant
➢ Component of the sample being assayed
➢ It consists in isolating from the sample the 1. It may be precipitated from solution
constituent to be determined in its pure 2. It may be a decomposition product
state and weighing it accurately. resulting from ignition of a compound
➢ The substance to be isolated maybe 3. It may be deposited on an electrode
1. The substance itself or by electrolysis.
2. Substance of known and definite
composition and which has a definite General Steps in Gravimetric
relation with the constituent to be Analysis:
determined.
➢ The substance to be isolated and weighed 1. Weighing the sample to be analyzed
may be obtained by: accurately
a. Direct ignition of the sample wherein by 2. Bringing the sample into solution using the
decomposition of the constituent most suitable solvent
another substance is left as residue 3. Precipitation of the constituent to be
o E.g., determination of the Bi2O3 determined based upon a reaction that
content of bismuth subnitrate. must proceed to completion.
4. Filtration using the appropriate medium
NORIENE MAIQUEZ 48
5. Washing the precipitate to remove

impurities which maybe adhering or NaCl+HNO3 → HCl+NaNO3
absorbed substance by products of the
reaction. 6HCl+2HNO3 → 3Cl2↑ + 4H2O + 2NO
6. Drying or ignition of the precipitate in a
tared crucible o Silver nitrate is added in excess to
7. Cooling and weighing of the precipitate or drive the reaction to completion
residue. through the common-ion effect
Basic Working Equation:

AgNO3 + NaCl → AgCl↓ + NaNO3
𝐰𝐭. 𝐨𝐟 𝐭𝐡𝐞 𝐫𝐞𝐬𝐢𝐝𝐮𝐞 𝐱 𝐆𝐅 𝐱 𝟏𝟎𝟎 o Precipitation must be performed
%𝐏 = away from strong light
𝐬𝐚𝐦𝐩𝐥𝐞
 Kapag given ang g/mol at may “yielded” na word sa problem.
▪ Silver chloride is
 GF is g/mol ng hinahanap divided by g/mol of product decomposed by sunlight
𝐠 𝐨𝐟 𝐫𝐞𝐬𝐢𝐝𝐮𝐞 𝐱 𝟏𝟎𝟎 with loss of chlorine
%𝐏 =
𝐠 𝐨𝐟 𝐬𝐚𝐦𝐩𝐥𝐞 o Diffused light the error chloride
 Kapag hindi givern ang g/mol pero hinahanap and %P ng which, if present, would pass
substance. through the filter.
𝐌𝐖 𝐬𝐚𝐦𝐩𝐥𝐞 𝐱 𝟏𝟎𝟎 o Precipitate is washed to remove
𝐌𝐖 𝐫𝐞𝐬𝐢𝐝𝐮𝐞 soluble salts present in the solution
chiefly sodium nitrate and x’ss
AgNO3
Determination of Chlorine in a o Washing with 0.01N nitric acid
Soluble Chloride prevents loss of AgCl through its
➢ Solution of a sample of a soluble chloride is return to colloidal condition
acidified with nitric acid and treated with (Peptization).
excess silver nitrate solution. o AgCl is appreciably VOLATILE when
➢ Other substances that form insoluble silver IGNITED, so it should be dried at a
salts must be absent from the sample. relatively low temp
o Reaction involved in the calculation
Assay of Sodium Chloride of amount of silver nitrate solution to
be used and of the purity of the
➢ Analyte: NaCl
sample.
o gmEW:
o MOLECULAR WEIGHT
➢ Titrant:
▪ NaCl = 58.44
➢ Indicator:
▪ AgNO3 = 169.87
➢ E.P.:
o Gravimetric Factor – or a chemical
➢ NOTES:
factor by use of which the weight of
o The solution is acidified with nitric
NaCl in the sample proportionate to
acid to prevent the precipitation of
the weight of AgCl formed can be
other substances insoluble in water
readily calculated
but soluble in nitric acid, such as
o Gravimetric method for
▪ Carbonates
determination of chlorine in a
▪ Oxides
soluble chloride can also be applied
▪ Phosphates
in the assay of most soluble
o Acid helps to coagulate any
▪ Bromides
colloidal silver chloride.
▪ Iodides
o Too great an excess of nitric acid
▪ Cyanides
must NOT be added.
▪ Thiocyanate
o Exerts some solvent action on silver
▪ As well as standardization of
halides.
HCl solns. and the estimation
o Acidified solution should NOT be
of silver cmpd.
heated until the silver nitrate has
been added, since chlorine may be
liberated and lost
NORIENE MAIQUEZ 49
o Volumetric precipitation method precipitating reagent slowly with

can be carried out more rapidly continuous stirring.
than gravimetric method o Coprecipitation occur in the
presence of nitrates, chlorates, and
Assay of Sodium Lauryl Sulfate for salt of iron, aluminum, chromium
and other trivalent element with
Sodium Sulfate Content BaSO4
➢ Analyte: Sodium Lauryl Sulfate
o gmEW: Na2SO4+BaCl2∙2H2O → BaSO4↓+2NaCl+2H2O
➢ Titrant: HCl
➢ Indicator: Barium Chloride TS
o It may apply to the estimation of
➢ E.P.:
metals that form insoluble sulfates
➢ NOTES:
such as Ba, Ca, etc.
o The soln of the sulfate is acidified
o Amount of CaO in MgCo3, Mg2OH,
with HCl to prevent ppt of
and MgO is determined by ppt of an
carbonate, which are soluble in HCl
equivalent amount of CaSO4 under
solution.
conditions such that MgSO4 remains
o Acid also increases the solubility of
in soln.
barium sulfate slightly and therefore
o Sulfur, free and combined, may be
promotes the growth of large
oxidized to sulfate and subsequently
crystals, since small crystals with
ppt as BaSO4.
greater surface area per unit of
o Combustion of sulfobromophthalein
weight dissolve more rapidly than
sodium in an oxygen flask
large one.
combustion with oxidizing agent
o Larger crystal with smaller surface
before the gravimetric
area exposed grow more rapidly
determination as carried out in the
than they dissolve.
assay of sodium lauryl sulfate.
o Soln. is heated to boiling to expel
o Thiosulfates, sulfites, persulfates, etc.,
dissolved CO2
may be estimated with similar
o Excess of hot BaCl2 soln. is added to
procedure.
ensure complete ppt and to
decrease the solubility of BaSO4 by
the common-ion effect.
Assay of Mercaptomerin Sodium
o Mixture allowed to stand overnight ➢ Analyte: Mercaptomerin Sodium
to allow the larger crystals to grow at o gmEW: 0.8622
the expense of the smaller ones. ➢ Titrant:
o BaSO4 is directed to be washed on a ➢ Indicator:
filter to remove excess BaCl2 and ➢ E.P.:
NaCl formed ➢ NOTES:
o Washing process may be carried out o The hydrogen sulfide reacts with the
more rapidly by washing once by mercuric salt which with the
decantation. formation of black mercuric sulfide
o The filtrate is always acidified with a as hydrogen sulfide is passed into
drop of HNO3 in carrying out the test the mixture.
for chlorides. o Mercuric sulfide is insoluble in acids,
o Coprecipitation is when BaSO4 hydrogen sulfide may be employed
exhibits the property of “dragging as the precipitating agent and HCl
down” some soluble salts when it is may be added to suppress the conc
precipitated. of sulfide ion so that metals which
o Occluded or coprecipitated salt form sulfides more soluble than
cannot be removed by ordinary mercuric sulfide and which may be
washing. present as impurities will not be
o Error from this source is reduced precipitated.
largely by precipitation from hot
dilute soln. and by adding the
NORIENE MAIQUEZ 50
o Ppt is washed with water to remove

soluble sulfides, then with alcohol to H3PO4 ↔ H+ + H2PO4-
remove water. H2PO4- ↔ H+ + HPO4-2
o Carbon tetrachloride, is added later HPO4-2 ↔ H+ + PO4-3
and is immiscible with water but
miscible with alcohol, can permeate
the ppt and dissolve any sulfur o Degree of ionization becomes less
formed by the oxidation of for each successive stage.
hydrogen sulfide. o Relative amounts of PO4-3, HPO4-2,
o Ppt is washed with carbon H2PO4- and H3PO4 in equilibrium
tetrachloride w/out suction to allow with one another depend on the
time for the sulfur, which is slowly hydrogen-ion conc of the soln.
soluble, to dissolve. o Basic soln PO4-3 and HPO4-2 ions
o Mercuric sulfide if volatile at high predominate.
temp (400°C). o Phosphate ion which exists in the soln
of the sample reacts with the Mg+2
ions contained in magnesia mxt to
HgCl2 + H2S → HgS + 2HCl
form the corresponding magnesium
salt; all these are more or less
o Same procedure can be adapted insoluble in water.
for the assay of other mercury salts, o Mg3(PO4)2, MgHPO4, and
antimony salts, and a preliminary Mg(H2PO4)2 may be formed.
oxidative degradation using acid o Addition of a soln NH4OH represses
permanganate, for the assay of the conc of H2PO4 and prevent the
other organomercury compounds formation of Mg(H2PO4).
such as meralluride. o Presence of the ammonium ion, the
salt is ppt as MgNH4PO4 → 6H2O
Determination of the Phosphate o If the soln is too basic Mg(OH)2 may
in Sodium Phosphate Solution be precipitated.
o Precipitation of both Mg3(PO4)2 and
➢ The phosphate is ppt as magnesium
ammonium phosphate, washed, dried, Mg(OH)2 is prevented by the
ignited to the pyrophosphate, and presence of ammonium salts
which, through the common-ion
weighed.
effect, act as a buffer and prevent
the hydroxyl-ion conc from
Assay of Sodium Phosphate Solution becoming too great.
o The hexahydrate, MgNH4PO4 →
➢ Analyte: Sodium Phosphate Solution
6H2O form relatively coarse crystals
o gmEW:
on standing for 3hrs or more in room
➢ Titrant:
temp.
➢ Indicator:
o At temp above 60°C the
➢ E.P.:
monohydrate is formed.
➢ NOTES:
o Ppt is washed with aqueous
o Magnesia mixture TS is a preparation
ammonia soln until free of chlorides.
containing magnesium ions in a
o Filtrate for chlorides, acidify with
buffered ammonium chloride-
HNO3 and add AgNO3 TS.
ammonium hydroxide soln.
o Upon ignition the magnesium
o Addition of a soln. containing
ammonium phosphate is converted
phosphate ions will form a ppt of
into the pyrophosphate.
magnesium ammonium phosphate
▪ if the pH of the reaction is
controlled, through buffering 2MgNH4PO4∙6H2O → Mg2P2O7 + 2NH3 + 13H2O
and the common-ion effect. 2Na2HPO4∙7H2O=2MgNH4PO4∙6H2O=Mg2P2O7
o Sodium phosphate is dissolved in
water, the phosphoric acid is ionized
NORIENE MAIQUEZ 51
o Each gram of Mg2P2O7 is equivalent lubricants that would be extracted along

to
2(268.07)
= 𝟐. 𝟒𝟎𝟗𝐠 of Na2HPO4∙7H2O. with the organic medicinal agent by the
222.55
solvent, chloroform or ether, which is used
o Same ppt MgNH4PO4→6H2O, result
subsequently.
when magnesium ions are treated
➢ Organic medicinal is basic
with a soluble dibasic ammonium
o Papaverine in papaverine HCl
phosphate.
➢ Or acidic
o The magnesium pyrophosphate
o Amobarbital in sodium amobarbital
obtained on ignition is equivalent to
tablets
the magnesium ammonium
➢ It is first extracted with an aqueous soln of
phosphate.
an acid or base to effect separation from
o Magnesium citrate soln was formerly
the neutral substances that might be
assayed by conversion to Mg2P2O7
present.
and is now assayed by a procedure
➢ Aqueous soln of the salt of the organic
involving the use of an organic
medicinal agent is then made alkaline or
precipitant.
acidic, as the case may be, and the
o The reagent, 8-hydroxyquinoline or
liberated organic base or acid is extracted
oxine selectively forms a very
with chloroform or ether.
insoluble precipitate
➢ If stearic acid or stearates are present, an
o Bismuth subnitrate is ignited to the
organic medicinal agent which is acidic
oxide, yielding an equivalent
(amobarbital) cannot be extracted with
amount of Bi2O3
NaOH soln because sodium stearate would
Notes: be extracted along with the salt of the
➢ The ff. are assayed gravimetrically in this organic acid.
way: ➢ Saturated soln of barium hydroxide is used,
o Gold sodium thiomalate and the insol barium stearate can be
o Aurothioglucose removed by filtration.
o Preparations of these cmpds. ➢ A preparation is acidified with a strong acid
▪ Zinc eugenol cement and such as HCl, the organic acid is liberated
zinc oxide with salicylic acid and may be extracted with an immiscible
are ignited to yield zinc solvent such as ether or chloroform.
oxide in the same way as ➢ Organic medicinal agent can sometimes
bismuth subnitrate, yielding be converted quantitatively to derivatives
bismuth oxide. by reactions involving some functional
▪ Aluminum monostearate on group such as
ignition yields an aluminum o Amino
oxide residue which is o Carboxyl
weighed directly. o aldehyde or ketone carbonyl
➢ Some miscellaneous gravimetric analyses in o phenolic hydroxyl, etc.
which official compound are converted to ➢ Insol salts formed by the reaction of amino
insoluble residues that are dried and or carboxyl groups may be included in this
weighed category.
o Barium sulfate converted to BaCrO4 ➢ Quaternary nitrogen cmpd will form insol
o Sulfurated potash is determined as salts with tetraphenylboron.
CuO ➢ These nitrogen-containing cmpd, choline
➢ Sometimes a loss in weight can be used as chloride, benzethonium chloride, and
basis for analysis bethanecol chloride, are easily assayed by
o Conversion of silicon dioxide, SiO2, ppt with sodium tetraphenylboron.
to silicon tetrafluoride, a gas, as in
the assay of magnesium trisilicate
R4N+ + B(C6H5)4- → R4N∙B(C6H5)4↓
for SiO2
➢ Before extraction of organic medicinal
agent, the sample of the powdered tablets
is frequently washed with petroleum benzine
to remove substances such as binders and
NORIENE MAIQUEZ 52

Pharmaceutical - Quality - Control Chap 1 10

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QUANTITATIVE PHARMACEUTICAL CHEMISTRY

▪ It must be checked against

o Normality – the number of gram

o Pipette – used to draw a definite

M – the molar ratio of the analyte versus the

Va – the pipetted-out volume of the analyte,

determined either in the natural state or in Notes 2:

➢ Good cleaning solution for glassware can

drug, or medicinal use and can Wash bottles

(Apparatus & Instrument)

2. SAMPLE PREPARATION ➢ Manifest themselves by slight variations in a

concentration or some other variables. measurement estimates underlying true

➢ The difference between the mean and the

➢ Find by dividing the absolute error by the

➢ Usually reported on a percentage basis by

➢ Calculated by finding the differences

and dividing by the number of

➢ Found by dividing the average deviation by

or as parts per thousand.

➢ Considered a better measure of precision

than average deviation.

➢ Other term: coefficient of variation

➢ Found by dividing the standard deviation by

➢ The difference between the largest and

The acetate ion, being a

▪ The hydroxyl-ion • Perchloric acids

(acidic & basic organic)

Topic 5: Ph calculation for

Topic 4: Ph calculation for strong

o To calculate the pH of a strong base • Clearing fractions by multiplying both sides

(acids) [H3O] = √𝑲𝒂[𝑯𝑨]

➢ Weak acids may be defined as proton

Rearranging and substituting

Clearing fractions by multiplying both sides by OH

Weak Bases, Charged Chemical

Weak Bases, Uncharged (Topic 8: salts)

Topic 10: Ph calculation for weak

be calculated using the ff.

Topic 11: Ph calculation for weak

➢ Solution of polyprotic bases contain all

Topic 12: degree of

being analyzed. equivalents for calculation purposes.

The chemical substance being analyzed o Ex.

concentration and usually added by mol (1 equiv) or 40.00 g of NaOH or

The act of adding and measuring the • The gram-equivalent of a chemical is

chemically equivalent to 1 gram-atom

at or very near the point in the titration defined as the weight of a

4. Replaces 1 gram-atom or ion

Theoretical point at which equivalent of hydrogen.

amounts of each have reacted.

Defined as GEW/1000. This term is used

change in some property of the reaction

➢ Thus, a solution of HCl may be standardized

Defined as the number of gram-

Defined as the number of gram- Topic 2: Chemical reactions used

milliequivalents involved in a quantitative

serve as the basis of titrimetric analysis are:

solute per liter (equiv/liter) or (solvent + solute)

solution in terms of moles per liter. 4. Complexation – produces

• The determination of the normality of

equal to a greater than 108

May be accomplished by the use of