Pharmaceutical Analysis 1 Lecture
Quality Control
- Evaluates, maintains and reference
standard for substances.
- Ensures correct labelling of containers
of materials and products.
- Ensures stability of active
pharmaceutical ingredients and product
is monitored.
- Helps investigate complaints relating to
product quality
- Participates in environment monitoring.
Quality
- Attributes / characteristics
- Compared to standard
- Basis for measuring the conformity
- Determines the degree of acceptability.
Measurable criteria:
1. Conformance - prescribed limits
2. Fitness for use - functionality of the
products
3. Reliability - function in the specified
environment for a prescribed length of
time.
4. Yield - high degree of acceptable units
produced
5. Customer satisfaction - requires the
product to be safe, pure and effective.
Drug quality as our main business
-The grim reality:
1. Poor quality medicines do not meet
official standards for: Strength, Quality,
Labeling, Purity, & Packaging
2. Poor quality drugs result in serious
health implications including
- Treatment failure
- Increased morbidity
- Development of drug resistance
- Adverse effects
- Mortality
- Wasted resources
Drug quality in the world:
➔ Availability of substandard and
counterfeit drugs in disturbing proportion
in many low-income countries.
➔ Lack of reliable drug quality assurance
systems in many developing countries.
Qualitative and Quantitative Pharmaceutical
Chemistry
Analytical Chemistry
● Qualitative - “What is in the sample?”
● Quantitative - “How much is present in
the sample?”
Quality control guarantees which reasonable
limits:
- Free from impurities
- Contains the amount of the active
ingredients stated on the label.
- Physical, chemically and
microbiologically stable.
- Provides optimal release of active
ingredients when the product is
administered
Quality control for quality drugs:
SHEWHART CYCLE - PDCA Approach (Plan,
Do, Check, Act)
Types of Analysis:
1. Based on sample size:
- Ultra Micro < 1mg
- Mirco: 1 - 10mg
- Semi micro: 10 - 100mg
- Macro: 100 - 1000mg
2. Based on extent of determination
a. Proximate - total amount of a
class/ group of active
constituent.
b. Ultimate - amount of a single
chemical species in a sample.
3. Based on the nature of methods:
a. Classical - Titrimetry,
Gravimetry.
b. Instrumental - Spectrometry,
Polarimetry
c. Miscellaneous - water content,
ash content, acid value (crude
drugs)
Standards and Monographs:
● USP / Phil Pharmacopoeia / NF
- A book of public pharmacopeial
standards
- Contains standards for
medicines, dosage forms, drug
substances, excipients,
medicinal devices, and dietary
supplements.
General Principles in Quality Control:
 Pharmaceutical Analysis 1 Lecture
● Accuracy (validity) - closeness to the
true value
● Precision (reliability) - closeness to each
other- reproducibility / repeatability.
Assignable causes for errors:
- Materials
- Methods
- Men
- Machine
Standards:
a. Pharmacopeial Standards
-found in published monographs
- USP/NF, BP,EP,PP
- Identity, physical tests, purity tests,
assay, limit tests
b. Regulatory Standard
- Mandated by regulatory
agencies
- Phil PDEA, WHO, US PDEA
- For regulation purposes.
c. In-house Standard
- Unofficial
- Generated by the manufacturer
- Allow flexibility
- Mandatory in compliance to
GMP.
Standards must cover the following points
1. Formula
- Ingredients, Amount
2. Raw material specification
- Characteristics, Permissible
range of purity, From the
monograph
3. Standard Operating Procedure
4. Finished Product Specification
- Proper performance, Purity,
Safety, Stability
5. Packing Material Standard
- Run on a high-speed line
- Involves a complicated assembly
- Functional
- Compatible with the product
- Protect the product and assure
stability
6. Test Methods
- Standardized and Validated
Quality Control - is a tool that gives the
assurance that a product/substance conforms
to standards and specifications through a
system of inspection, analysis and action.
Analytical Chemistry - branch of chemistry that
involves separating, identifying and determining
the relative amounts of the components in a
sample of matter.
- Qualitative Analysis - reveals the
chemical identity of the species in the
sample.
- Quantitative Analysis - establishes the
relative amount of one or more species
in the sample.
6 broad areas of applications:
1. Establish economic value
2. Determining health hazards
3. Diagnosis of disease
4. Controlling quality
5. Relating properties to
composition/structure
6. Conducting research
General methods of analysis (used in official
pharmaceutical analysis):
A. Volumetric/Titrimetric
- Neutralization methods (in aqueous and
nonaqueous solvents)
- Precipitimetry or Precipitation or
Saturation methods
- Complex Formation (Complexation)
methods
- Oxidation-Reduction (REDOX)
methods
1. Neutralization
a. Alkalimetry - titration of acid with
standard alkali solution.
b. Acidimetry - titration of base with
standard acid solution.
2. Precipitation
- A substance is titrated by
precipitating it with a standard
solution of a precipitating agent.
- Based on reactions that yields
ionic compounds of limited
solubility.
3. Complex Formation Methods
- A substance is titrated by with a
standard reagent to the
formation of a complex ion.
 Pharmaceutical Analysis 1 Lecture
B. Gravimetric - based on weight -water soluble
measurements -reacts stoichiometrically with the
C. Special Methods (Drug Analysis) sample
a. Ash and water determination -with fairly-high equivalent
b. Extractive and crude fiber content weight.
c. Fats, fatty oils, waves, balsams b. Secondary Standard - solution
d. Volatile oils that is not necessarily pure, but
e. Alkaloids and amine drugs whose exact concentration is
Steps in a Quantitative Analysis: known.
1. Selecting a method of analysis Standardization - process of determining
2. Sampling the exact concentration of a solution.
3. Preparing the laboratory sample 3. Indicator - substance that changes in
4. Defining replicate samples color when passing from one medium to
5. Dissolving the sample another or a reagent that changes color
6. Eliminating interferences at a point when equivalent amounts of
7. Treating the sample and measuring the reacting substances have already
analyte reacted.
8. Calculating the amount and evaluating 2 types of endpoint:
the results. a. Practical / Experimental Endpoint -
Quantitative Method of Analysis: shown by change of color of solution
● Black Determination being titrated.
- All steps of the analysis are b. Theoretical / Stoichiometric Endpoint /
performed in the absence of the Equivalence Point - equivalent amount
sample. of substances have already reacted.
- Used to correct errors due to Rules for the use of indicators:
contaminations 1. Use 3 drops of indicator test solution for
- Performed simultaneously with a titration unless otherwise directed
actual determination. 2. Strong acid (Methyl Orange, Methyl
● Parallax Error Red, or Phenolphthalein) + Strong Base
- Error in reading due to optical 3. Weak acid + Strong base
illusion. (Phenolphthalein)
Titration - process whereby a standard solution 4. Weak base + Strong acid (Methyl Red)
is made to react with a sample in solution in the 5. Weak base should never be titrated with
presence of an indicator until the endpoint is a weak acid or vice versa, since no
reached. indicator will give a sharp end point.
Apparatus: Burette 6. The appearance of a color is more
Components of Titration: easily observable than it’s
1. Analyte - substance being analyze disappearance. Therefore, always titrate
2. Standard solution - reagent whose exact where possible to the appearance of a
concentration is known and that is used color.
in volumetric analysis.
a. Primary Standard - an ultra-pure
Indicator Ph Acid Base End
compound in solid form used as Point
standard.
Properties of Primary standard: Methyl 3.2 - Pink Yellow Peach /
-chemically-pure Orange 4.4 Salmon
-chemically-stable
Methyl 4.2 - Red Yellow Peach /
-easily prepared Red 6.2 Salmon
 Pharmaceutical Analysis 1 Lecture
Phenolp 8.0 - colorless Fuschia Light
hthalein 10.0 / Red Pink

Types of Titration:
1. Direct Titration - titration in which the
substance to be measured is directly
determined by titration to an end point
with a standard solution.
2. Indirect Titration - titration which
employs a preliminary reaction in which
the analyte is replaced by equivalent
amount of another substance which is
determined by titration.
3. Residual or Back Titration - titration
which involves the addition of an excess
titrant.