Quality Control of Crude

Drug

Prof.(Dr.) U.S. Mishra

Dept.(P.A.&Q.A)
Quality Control
Quality control of crude drug mainly include
the standardization and evaluation method.
 Standardization means determination of
quality,purity,potency,efficacy andsafety
 Evaluation means confirmation of identity
 The synonym of quality control is assay of
active constituents followed by official
standards.
Standards of Identity&Purity
 Standards of Identity-These includes:-
 Organoleptic
 Microscopical/Histological character
 Deterioration of drug on storage
 Chemical tests
Standardization and Evaluation
Before a drug can be evaluated a sample must
be drawn for analysis.
 Sample is truely representative
 Different method of sampling is done from
large quantity of bulky drug
Methods of Evaluation
 Organoleptic Evaluation
 Microscopical Evaluation
 Physical Evaluation
 Chemical Evaluation
 Biological Evaluation
 Organoleptic Evaluation-It includes
colour,odour,taste,size,shape and surface
characteristic
 Microscopical Evaluation-It is important for
organized crude drug having definite cellular
structure
 Chemical Evaluation-This include chemical
tests
 Biological Evaluation
 Physical Evaluation:
1. It include-foreign analytical method,microbial
contamination,moisture content(loss on
drying,vaccum drying)
2. Ash values-Total ash values,Acid insoluble
ash,water soluble ash,sulphated ash
3. Extractive values-water soluble
extraction,ethanol extraction,pet.ether
extraction,ether extraction,volatile oil
determination
1. Physical parameter-M.P&B.P,R.I,Optical
rotation,Rf values
2. Spectroscopy method-UV,IR,NMR,MS,X-
RAY
3. Chromatographic method-
TLC,HPLC,HPTLC,GC
ASH VALUES
 Total ash-Place 2-4gm grounded material in a
crucible ↓
 Ignite it at 500-600ºc(until white)
 ↓
 Cool in a desicator and weigh it
 If carbon free ash can’t obtained,then cool the
residue with 2ml of water or saturated soln of
amm.nitrate
 ↓
 Dry on a waterbath,then on a hot plate
Ignite to constant weight
↓
Allow the residue to cool in a desicator(for
30mins)
↓
Weigh without delay & calculate the total ash
mg per gm
Acid Insoluble Ash
Total ash+25ml HCL cover with a watchglass
↓
Boil for 5 minutes
↓
Rinse the watchglass with 5ml hot water,add
liquid to the crucible
↓
Collect the insoluble matter on an ashless filter
paper&wash with hot water
 ↓
Transfer the insoluble matter to original
crucible
↓
Dry on hot plate & ignite to constant weight
↓
Cool the residue for 30 mins
↓
Weigh without delay,calculate the weight
Water Soluble Ash
Total ash+25ml of water
↓Boil for 5 min
Collect insoluble matter in a crucible on an ashless
filterpaper
↓wash with hot water
ignite for 5min at 450ºc
↓
Weight of total ash­weight of this residue
↓
Calculate content water soluble ash
Extractive Value
 This determines the amt. of active
constituents extracted with solvent
 Recommended Procedure-
 Method-1:Hot extraction-
4gm powdered drug +100ml water
↓weigh to obtain total
wt(flask)
Shake well,allow to stand for
1hour
 ↓
Attach reflux condenser to the flask
↓boil for 1hour,cool&weigh
Readjust to original total weight with solvent
↓shake well & filter it
Transfer 25ml of filtrate to tared flatbottomed disk

↓Evaporate to dry
Dry at 105ºc for 30min
↓cool in a desicator for 30min
Weigh& calculate the extractable matter
 Method-2:Cold Maceration-
4gm powdered material macerate with 100ml of solvent
for 6 hours
↓ shaking frequently
Allow to stand for 18 hours
↓ Filter it
Transfer 25ml to the tared flat bottomed disk
↓ Evaporate to dry
Dry at 105ºc for 6hours
↓cool it for 30min
Weigh & calculate the extracted matter
Determination of crude fibre
 Estimation of crude fibre denotes the
measurements of content of
cellulose,lignin,corkcells in plant tissue
 This is used for microscopic examination of
cellular materials(e.g.determine oleo-resin
&starch in ginger)
 It is also used for detection of presence of
adulterants
PROCEDURE
2gm of crude drug→Ether
extract+200ml1.25%H2So4(in 500ml)
↓Reflux for 30min
Filtration and residue washed with boiling water
↓until free from acid
Residue is rinsed back into flask with 200ml of
boiling 1.25%NaOH soln
↓boil for 30 min
Filter the liquid
 ↓
Residue on the filter is washed with boiling
water until neutral
↓
Dried at 110ºc to constant weight
↓
Incinerated to constant ant weight
 %of original wt of material ═ wt of dried
residue- wt.of incinerated residue
ASSAYS
 A crude drug may be assayed for a particular
group of constituents e.g. total alkaloids in
belladona or total glycosides of digitalis
 Biological assays is time-consuming and
applicable to those potent drugs
 The physical and chemical assays are
employed for routine standardization.
Types of assay employed for crude
drug
 Types of Assay  Examples
1. Separation & weighing  Colchicine from
of active constituents colchicum
 Total balsamic esters of
peru balsam
2. Chemical  Total alkaloid of many
drugs
 Strychnine from
nuxvomica
3. Physical
 Cineole in Eucalyptus
oil
 Spectrometric including  Most group of active
colorimetric & constituents
flouroscence
 Biological  Cardioactive
drugs,antibiotics,vitamin
s,antitumour drugs
 Radio Immuno Assay  Hespridin,morphine,trop
ane alkaloids,
vincristine
 Enzyme immuno assay
 Quassia,podophyllotoxi
ns
Spectroscopic Analysis
 The electromagnetic vibration utilized in
spectroscopic analysis
 This can be divided according to wavelength
into uv,visible,near IR & IR regions
 For this evaluation a substance of std. curve
is prepared by measuring the optical
densities
 The solution must be sufficiently diluted
Fluoroscence Analysis
 Many substances e.g.quinine in solution in
dilute sulphuric acid emit light of different
wavelength.
 For examination solids may be placed directly
under the lamp whereas liquid may be
examined in non-fluorocent dishes or test
tube or after spotting on filter paper
Quantitative fluoroscence analysis
 This tech. utilizes the fluoroscence produced
by a compound in uv light for quantitative
evaluation
 The instrument employed is a
fluorimeter,consists of uv source and
photoelectric cell to measure the intensity of
emitted light.
NMR
 This tech.is associated with structure
determination of organic compounds
 The use of H NMR has been described for
the assay of atropine and hyoscine in extract
of belladona,hyocyamus & stramonium
 IMMUNOASSAY- Used for quantitative
determination of compounds in biological
fluids.
RIA
 The assay depends on the specific reaction of
antigen and certain antibody
 Used in clincal analysis
 Example-Digitalis
ELISA-
Competition for an immobilized Ab takes place with a
modified form of the compound under
analysis(enzyme bounded)
↓
Release of compound-enzyme complex from binding
site(e.g.Alkaloid drugs)
Tandem mass spectroscopy(MS-MS)
 Mass spectroscopy is usually associated with
the structural elucidation of compounds
 By the two mass spectrometers it is possible
to determine quantitatively the amount of a
particular targeted compound incomplex
mixtures
e.g.used for analysis of cocaine in plant
material