Quality Control & Assurance With Instrumentation

QUALITY CONTROL 1
JENKINS’ QUANTITATIVE PHARMACEUTICAL

CHEMISTRY
by
Adelbert M. Knevel & Frank E. Digangi
1|Page
QUALITY CONTROL & ASSURANCE WITH INSTRUMENTATIONS
QUALITY
Sum of all factors which contribute directly or indirectly to the safety, effectiveness and
reliability of the product.
Serve as a basis for measuring the uniformity of the product and determines its degree of
acceptability.
Quality control guarantees within reasonable limits that a product is:
1. Free from impurities
2. Physically and chemically stable
3. Contains the amount of active ingredients stated on the label
4. Provides optimal release of a.i. when the product is administered.
Official Compendia
Approved sources of guidelines for drug quality required by certain practitioners or

agencies
Product monograph:
1. Chemical structure
2. Chemical name
3. Purity rubric
4. Packaging and storage
5. Reference standard
6. Identification tests
7. Corresponding tests for chemical and physical constants
8. Water content
9. Assay procedure
2|Page
CALCULATIONS OF RESULTS AND ERRORS
Source and Nature of Errors
The discrepancies in the results are caused by various sources of error to which all
experimental data are subjected:
Indeterminate Errors
Slight variations in a series made by the same observer under identical conditions. They
result from causes difficult to detect, such as differences in the judgment and skill of the analyst.
They are intangible and elimination is impossible.
Determinate Errors
Can be determine and their value can reduce on the final results.
They arises from causes such as:
1. Personal errors made by the individual analyst.
2. Errors of method caused by faulty procedure.
3. Apparatus errors due to poor construction or calibration
Accuracy and Precision
Accuracy
Is used to denote the agreement of an experimental result of a series of experimental

results with true value.
Absolute Error
Difference between the mean and the true value.
Relative Error
Found by dividing the absolute error by the true error.
Precision
A measure of reproducibility of data within a series which agree closely with one another.
3|Page
Average Deviation
Calculated by finding the differences between individual results and the mean, regardless
of sign, adding these differences and dividing by the number of determination.
Relative Ave. Dev.
Found by dividing the average deviation by the mean.
Standard Deviation
√∑(𝑥−𝑥)2
𝑠=
𝑛−1
Relative Std. Dev.
Found by dividing the average deviation by the mean X 100.
Range
The difference between the largest and smallest results in the series of measurements.
Significant Figures
Defined as all certain digits of measurement plus one doubtful digit.
Rules of Significant Figures:
1. All non zero are significant.
2. Zeros between non-zero digits are significant
3. Leading zeros to the left of the first non zero digits are not significant, such zeros merely indicate
the position of the decimal point.
4. Trailing zeros that are also to the right of a decimal point in a number are significant.
5. When a number ends in zeros that are not to the right of a decimal point, the zeros are not
necessarily significant.
4|Page
SAMPLING
Act of drawing out samples from a given batch of materials or product.
Fixed rules cannot be laid down in sampling, for much depends on the nature of the
material and the quantity from which a representative sample is to be taken.
Bulk quantities of chemicals and drugs may be sampled by the methods given in the USP
for sampling vegetable drugs:
1. When the components parts are less 1cm in any dimension, and that when the total weight of
the drug to be sampled is less than 100kg at least 250g shall constitute an official sample. When
the drug to be sample is excess of 100kg, samples shall be taken with the above method mixed
and quartered, two of the diagonal quarters being rejected. The remaining two quarters being
combined and again subjected to a quartering process in the same manner until two quarters
weigh at least 125g. Two quarters then constituting as an official sample.
2. When the components parts are over 1cm in any dimension, and that when the total weight
of the drug to be sampled is less than 100kg at least 500g shall constitute an official sample.
When the drug to be sample is excess of 100kg, samples shall be taken with the above method
mixed and quartered, two of the diagonal quarters being rejected. The remaining two quarters
being combined and again subjected to a quartering process in the same manner until two
quarters weigh at least 250g. Two quarters then constituting as an official sample.
3. When the total weight of a drug to be sampled is less than 10kg, it is recommended that the
above methods be followed but that somewhat smaller quantities be withdrawn, and in no case
shall the official sample weighs less than 125g.
4. As an alternative to withdrawing of official samples according to the methods 1, 2, 3 the official

sample may consist of the total amount of a direct purchase made by officials charged with
enforcement of a federal, state, or municipal food and drugs act.
Square Root System
Military Standard Table
ASSAY
Process of determining the potency, strength or percentage purity of a drug preparation.
5|Page
Qualitative Analysis
Process of determining the elements or compounds present in the given sample.
Quantitative Analysis
Process of determining the proportions in which the various elements or compounds are
present.
METHODS OF ANALYSIS IN QUANTITIVE PHARMACEUTICAL CHEMISTRY
VOLUMETRIC ANALYSIS
A.K.A Titrimetric Analysis Determination of the volume of a solution of known

concentration required to react with a given amount of the substance to be analyzed.
Titration
Act of adding and measuring the volume of titrant used in the assay
Analyte
Chemical substance being analysed
Primary Standard
Substance of known purity and use to standardize solution.
𝑔 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
N = 𝑚𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡×𝑚𝐸𝑞 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
Requirements for primary standard:
1. Must be easy to prepare and pure
2. Must be definite known composition
3. Must be stable
4. Must react stoichiometrically with the substance present in the solution
5. Must be soluble in water
6|Page
6. Must have fairly high equivalent weight
Primary standards for acids:
1. Anhydrous sodium carbonate
2. Calcium carbonate
3. THAM
4. Mercuric oxide
Primary standards for alkalis:
1. Potassium biphthalate
2. Benzoic acid
3. Sulfamic acid
4. Potassium biiodate
5. Sodium carbonate
Secondary Standard
Accomplished by the use of another standard solution.
Substance that is not necessarily pure but whose exact purity is known
N1V1 = N2V2
Titrant
Solution of known concentration
Standard solutions
Solution of known concentration.
7|Page
Standardization
Determination of the concentration of a standard solution.
Gram-equivalent weight (GEW)
Defined as weight in grams which is chemically equivalent to 1 gram-atom of hydrogen.
In neutralization reactions it is defined as weight of a substance in grams which contains,

furnishes, react directly or indirectly or replaces 1-gram-atom or ion of hydrogen.
Gram-milliequivalent weight (GmEW)
Defined as GEW/1000
Equivalent
Defined as the number of gram equivalents involved in a quantitative procedure.
Milliequivalent (mEq)
Defined as the number of gram milliequivalents involved in a quantitative procedure.
𝑀.𝑊.𝑜𝑓 𝑎𝑛𝑙𝑦𝑡𝑒
mEq =
𝑓×1000
Titer
Is the strength in grams per mL of solution or the weight of a substance chemically

equivalent to 1mL of a standard solution
Concentration of a Standard Solution can be expressed in terms of:
Normality
Concentration expressed as number of equivalents of solute per liter or milliequivalent

per milliliter of solution.
N = 𝑚𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡×𝑚𝐸𝑞 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
𝑡𝑖𝑡𝑒𝑟 𝑣𝑎𝑙𝑢𝑒
N = 𝑚𝐸𝑞 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
N=𝑀 ×𝑓
8|Page
Molarity
Concentration of solution in terms of moles per liter.
𝑔 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒
moles = 𝑀.𝑀. 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒
𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒
M= 𝐿 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
M=
𝑀.𝑀 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 ×𝐿 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
𝑁𝑜𝑟𝑚𝑎𝑙𝑖𝑡𝑦
M= 𝑓
Molality
Contains a mole in one thousand grams of solution
m=
𝑀.𝑊.×𝑘𝑔 𝑜𝑓 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
Indicator
A chemical which changes color at or very near the end point where equivalent quantities
of analyte and titrant have reacted.
Indicator pH Range Acid Base

Methyl violet 0.0-1.6 Y V
Malachite green 0.0-2.0 Y G
Methyl yellow 2.9-4.0 R Y
Bromophenol 3.0-4.6 Y B
blue
Methyl orange 3.2-4.4 P Y
Bromocresol 4.0-5.4 Y B
green
Methyl red 4.2-6.2 R Y
9|Page
Bromocresol 5.2-6.8 Y P
purple
Bromothymol 6.0-7.6 Y B
blue
Phenol red 6.8-8.2 Y R
Cresol red 7.2-8.8 Y R
Thymol blue 8.0-9.2 Y B
Phenolphthalein 8.0-10.0 C.L R
Thymolphthalein 9.3-10.5 C.L B
Lithmus paper 5.0-8.0 R B
Alizarin yellow 10.1-12.0 Y R
Rules for the use of Indicators:
1. Use 3 drops of indicator test solution for a titration unless otherwise directed.
2. When strong acid is titrated with strong alkali and vice versa, Methyl orange, Methyl red or
phenolphthalein may be used.
3. When weak acid is titrated with a strong alkali, use Phenolphthalein as indicator.
4. When weak alkali is titrated with a strong acid, use Methyl red as indicator.
5. A weak alkali should never titrated with weak acid or vice versa, since no indicator will give a
sharp end point.
6. The appearance of color is more easily observable than disappearance. Always choose if
possible the appearance of color.
Mixed Indicators
Some indicators do not give sharp end points. In such cases mixed indicators are used to
sharpen up the color change.
10 | P a g e
Examples:
Xylene cyanol-Methyl orange
Bropmocresol green-Methyl red
Bromocresol green-Chlorophenol red
Cresol red-Thymol blue
Thymol blue-Phenolphthalein
Endpoint
Shown by the change of color of the solution.
Stoichiometry
Branch of chemistry pertaining to numerical relationships of chemical elements and

components and mathematical proportions of products and reactants
Steps:
1. Determine the moles of the given quantity of product
2. From the amount of the product, calculate the amount of the reactant consumed
3. Convert the amount of reactant from step 2 to mass, in grams using the molar mass of the
reactant as the conversion factor.
*the chemical equation of both the reactant and the product should always be balance
Formula:
𝑔 𝑜𝑓 𝑔𝑖𝑣𝑒𝑛 𝑚𝑜𝑙𝑒 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒

g of sample = 𝑀.𝑊.𝑜𝑓 𝑔𝑖𝑣𝑒𝑛 × 𝑚𝑜𝑙𝑒 𝑜𝑓 𝑔𝑖𝑣𝑒𝑛
× 𝑀. 𝑊. 𝑜𝑓 𝑡ℎ𝑒 𝑠𝑎𝑚𝑝𝑙𝑒
Chemical Reactions Used In Volumetric Analysis:
Neutralization Reaction Method
Chemical processes in which an acid (proton donor) reacts with base (proton acceptor).
11 | P a g e
Based on titrant used:
Acidimetric Analysis
Analysis of a base using an accurately measured volume of an acid.
Alkalimetric Analysis
Analysis of an acid using an accurately measured volume of a base.
Based on the number of titrant used:
Direct Titration
Made to react continuously with the analyte until chemically equivalent amounts of each
have reacted or have reached the end point.
𝑁×𝑚𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡×𝑚𝐸𝑞 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒

% purity = 𝑔 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
× 100
Residual / Indirect Titration
A known volume of standard solution is added and known to be in excess is titrated with
another standard solution.
(𝑁1𝑉1−𝑁2𝑉2)×𝑚𝐸𝑞 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
× 100
Double Indicator
Making use of two endpoints in single titrations
Procedure for Double Indicator Method using one sample:
- An accurately weighed sample is dissolved in 40mL of distilled water

- Add 2-3 drops of phenolphthalein
- Titrate with 1N hydrochloric acid until the pink color is discharged
- Record the volume of hydrochloric acid until the pink color is discharged
- Record the volume of hydrochloric acid consumed
- To the resulting mixture, add 2-3 drops of methyl orange
- Titrate with the acid until the end point is reached
12 | P a g e
- The volume of the acid consumed is recorded
- Compute for the percentage purity of the component of the mixture
If the volume of HCl consumed in Pp is greater than the volume consumed in Mo titration =
OH&CO3
(𝑚𝐿 𝐻𝐶𝑙 𝑃𝑝−𝑚𝐿 𝐻𝐶𝑙 𝑀𝑜)×𝑁 𝐻𝐶𝑙×𝑚𝐸𝑞

%OH = 𝑔 𝑜𝑟 𝑚𝐿 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
× 100
2 (𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙 𝑀𝑜)×𝑁 𝐻𝐶𝑙×𝑚𝐸𝑞

%CO3= × 100
𝑔 𝑜𝑟 𝑚𝐿 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
If the volume of HCl consumed in Pp is less than the volume consumed in Mo titration =
CO3&HCO3
(𝑚𝐿 𝐻𝐶𝑙 𝑀𝑜−𝑚𝐿 𝐻𝐶𝑙 𝑃𝑝)×𝑁 𝐻𝐶𝑙×𝑚𝐸𝑞

%HCO3 = × 100
𝑔 𝑜𝑟 𝑚𝐿 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
2 (𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙 𝑃𝑝)×𝑁 𝐻𝐶𝑙×𝑚𝐸𝑞

%CO3= 𝑔 𝑜𝑟 𝑚𝐿 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
× 100
Procedure for Double Indicator Method using two samples:
- An accurately weighed sample is dissolved in 40mLof distilled water

- Add 2-3 drops of phenolphthalein
- Titrate with 1N hydrochloric acid until the pink color is discharged
- Record the volume of hydrochloric acid until the pink color is discharged
- Record the volume of hydrochloric acid consumed
- To the resulting mixture, add 2-3 drops of methyl orange
- Titrate with the acid until the end point is reached
- The volume of the acid consumed is recorded
- Compute for the percentage purity of the component of the mixture
Precipitation / Argentometry Method
Silver nitrate Ammonium thiocyanate

P.STD NaCl S.STD AgN O3
INDICATOR Eosin Y TS FAS TS
ENDPOINT Formation of ppt Reddish Brown
MET. OF AN. Fajan’s Method Volhard’s Method
BURETTE Mohrs / Base Geissler / Acid
13 | P a g e
Disadvantages:
1. Co precipitation effect do not give the real precipitate of the substance
2. The choice of appropriate indicator is very limited
3. 4 cardinal parameters that precipitimetry is feasible
* precipitation formed is insoluble
* precipitation method is rapid and fast
* co precipitation effect must be minimal
* detection of equivalence must be minimal
End point can be determined by:
- Cessation of precipitation or appearance of turbidity

- Instrumental methods
- Use of internal indicators
Types of Indicator Use:
Ferric Ammonium Sulfate TS
- Used both in direct and indirect titrations employing standard ammonium thiocyanate
- The thiocyanate reacts with silver or mercuric ions present to form white precipitate of
silver or mercuric thiocyanate but as soon as all the silver or mercury has been
precipitate, its thiocyanate ion reacts by ferric ammonium sulfate to form a red ferric
thiocyanate.
- First appearance of red color marks the endpoint.
Potassium Chromate TS
- Forms a red precipitate of silver chromate
Adsorption Indicators
Dichlorofluorescein TS
Eosin Y TS
Tetrabromophenolphthalein Ethyl Ester
14 | P a g e
- Prepare this solution fresh
- Used in the analyses of halides by direct titration with silver nitrate
- Endpoint is indicated when the color of the silver halide precipitate changes abruptly
- Color change are best in diffuse light condition
Methods of Precipitation:
Volhard’s Method
- Colored ion method

- FAS TS as indicator
- NH4 Fe(SO4)2 + 2H2O
- Used for thiocyanate titrations
Mohr’s Method
- Formation of secondary precipitate

- Potassium Chromate TS as indicator
- Used for halide titrations
Fajan’s Method
- Change color of precipitate

- Dichlorofluorescein TS, Eosin Y TS, Tetrabromophenolphthalein Ethyl Ester as an
indicator
- Used for potassium chloride titrations
Gay Iussac Method
- Cessation of preicipitate/Flocculation
- NaCl as precipitating agent, no indicator
- Not reliable method
Liebig’s Method
- Sodium tetraphenylboron as STD. SOLN

- Potassium biphthalate as P.STD.
- Turbidity as an endpoint
- Used for organic N compds. Titrations
Formula:
Normality:
15 | P a g e
𝑀.𝑊.𝑜𝑓 𝑝𝑝𝑡 𝑎𝑔𝑡
N = 𝑤𝑡 𝑜𝑓 𝑝𝑝𝑡 × 𝑀.𝑊.𝑜𝑓 𝑝𝑝𝑡
÷ (𝑚𝐸𝑞 × 𝑚𝐿)
Direct Titration

× 100
Residual Titration
% purity = × 100
Complexometry Method
A process based on the formation of a complex substance in the course of analysis
EDTA
P.STD CaCO3
INDICATOR Hydroxynaphthol blue
ENDPOINT Appearance of deep blue color
MET. OF AN. Complexometry Method
BURETTE Geissler / Acid
Complex
The resulting compd. when a metal ions combines with a molecule which donates
electron
Chelates
A combining molecule that contains 2 or more groups that donate electrons.
Form water soluble complex with metal ion
16 | P a g e
Chelating agents
Form complexes which are insoluble in water but soluble in organic solvents
Sequestering agents
Applied to chelating agents that form water soluble complex with metal ion.
Ligand
Electron pair donor or Lewis pair and has the ability to bind with the metal ion and
produce a complex ion
Classification of Ligand:
1. Monodentate
2. Polydentate
Qualities of a god Indicator for complexometry:
1. Sharpness of color change at the endpoint
2. Specificity of indicator for the metal ion under the conditions of the analysis
3. Stability constant is smaller than that of the metal-EDTA complex
4. Gives up the metal ion to the titrant EDTA for complexing
5. Should not compete with the EDTA
Metals detected by the Indicator:
indicators End point Metal Ions detected

Mordant black II Ca, Ba, Mg, Zn, Cd, Mn, Pb, Hg
Eriochrome black T
Solochrome black T R–B
17 | P a g e
Murexide (ammonium
purpurate) V–B Ca. Cu. Co
Catechol violet V–R Mn, Mg, Fe, Co, Pb
Methyl blue B–Y Pb, Zn, Cd, Hg
Thymol blue B – GRY Pb, Zn, Cd, Hg
Alizarin R–Y Pb, Zn, Cu, Mg, Co
Sodium alizarin B–R Al,Thorium

sulphonate LMN – Y Bi,Thorium, Pb, Zn, Cd, Hg
Xylenol orange
* the indicator used is hydroxynaphthol blue for calcium containing compds.
*eriochrome black TS is used for zinc compds. and their preparations
Types of Complexometry Method:
Direct Titration
The most convenient and simplest method which is similar to acid-base titrations
Example:
- Assay of calcium chloride

- Analysis of: Cu, Mn, Ca, Ba, Br, Zn, Cd, Hg, Al, Sn, Pb, Fe, Mo, Co, Ni, V, Ga, Cr, Bi
Residual / Back Titration
- Std. EDTA solution is added to the metal soln, which is to be analysed and the excess is
back titrated
Example:
- Determination of Manganese
Replacement / Substitution Titration
- The metal to be analysed displaces the metal that form complexes
Indirect Titration
18 | P a g e
- Determination of ions such as anions which do not react with EDTA
- Protons from disodium EDTA are displaced by heavy metal and titrated with sodium
alkali
Example:
- Assay of barbiturates using mercuric ion solution
EDTA
Unselective reagent because it form complexes with numerous charged cations
Disodium salt is preferred over the free acid in preparing standard solution of EDTA. Why?
- More water soluble

- Non – hygroscopic
- Very stable
C10H16N2O8 . 2H2O = 372.24 g/mol
Factors that increases EDTA selectivity:
1. Use of masking and de-masking agent
Masking – the term used to indicate the determination of a metal in the presence of
another metal.
2. pH control
Based on the differences in stability of the chelates formed between the metal ions and
the chelating agent.
The stability of metal complex is pH dependent
3. Use of selective metal indicator
The indicator chosen should be sufficiently rapid to permit establishment of the end point
without undue waiting.
4. Classical separation
These mat be applied if they are not tedious, thus the following precipitates may use for
separations in which after being re-dissolved, and the cations can be determined
compleximetrically.
19 | P a g e
5. Solvent extraction
6. Removal of anions
7. Kinetic masking
This is a special case in which a metal ion does not effectively enter into the complexation
reaction because of its kinetic inertness.
Application of Complexometry:
1. Compleximetry is widely used in the medical industry because of the microliter size sample
involved. The method is efficient in research related to the biological cell
- Ability to titrate the amount of ions available in a living cell.
- Ability to introduce ions into a cell in case of deficiencies
2. Compleximetric titrations is an efficient method for determining the level of hardness of water
caused by accumulation of metal ions
- Hardness in water is caused by the presence of calcium and magnesium salts.
- Temporary hardness is caused by the bicarbonate of their elements and can be

destroyed by boiling
- Permanent hardness is caused by sulfates and chlorides of calcium and magnesium and
cannot be affected by boiling
- Total hardness is represented by the combined temporary and permanent hardness and
can be determined by titration with EDTA
Formula:
𝑀 𝑜𝑓 𝐸𝐷𝑇𝐴 𝑀.𝑀 𝑜𝑓 𝑠𝑥 1000𝑚𝑔

mL of EDTA = 1000𝑚𝐿
× 𝑚𝑜𝑙𝑒
× 1𝑔
Direct Titration
Using Normality

× 100
Using Molarity
20 | P a g e
𝑀×𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡×𝑀.𝑚𝑎𝑠𝑠 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
× 100
Using Titer Value
T.V. = N × mEq
T.V. = M × M.mass
𝑁×𝑚𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡×𝑇.𝑉.𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒

× 100
𝑀×𝐿 𝑜𝑓 𝑡𝑖𝑡𝑟𝑎𝑛𝑡×𝑇.𝑉.𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒

% purity = × 100
Residual Titration
Using Normality where V = mL
× 100
Using Molarity where V = L
(𝑀1𝑉1−𝑀2𝑉2)×𝑚𝐸𝑞 𝑜𝑓 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
% purity = × 100
Hardness of Water
Temp. H. = bicarbonates and carbonates
Prem. H. = sulfates and chlorides
𝑤𝑡
ppm = 𝑀.𝑊. × 100
TH = TEMP. H. + PERM. H.
Hardness in Terms of CaCO3
𝑀.𝑀.𝑜𝑓𝐶𝑎𝑙𝑐𝑖𝑢𝑚 𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒
Strength in mg/L = 𝑀.𝑊.𝑜𝑓 𝑠𝑥
Conc. CaCO3 Indication

0 – 60 mg/L Soft
61 – 120 mg/L Moderate
21 | P a g e
121 – 180 mg/L Hard
>180 mg/L Very hard
Oxidation – Reduction Method
Chemical reaction in which the oxidation states of a certain atom change
Reactions in which electrons are transferred between reactants
The simplest type of these reaction is the direct combination of elements
Faraday’s Law
States that a change of one is equal to the gain or loss of 96,500C of electricity of each
formula weight of element or group of elements involved
Reducing Agents
The reactant that loses electrons in REDOX reaction. A substance that causes the
reduction of an element or compd.
𝑦𝑖𝑒𝑙𝑑𝑠
1. Oxalate ion → Carbon dioxide
C2O4-2 → 2CO2 + 2e
2. Thiosulfate ion → Tetrathionate ion
2S2O3-2 → S4O6-2 + 2e
*two thiosulfate ions must lose two electrons in forming one tetrathionate ion or each
thiosulfate ion loses one electron
3. Arsenite ion → Arsenate ion
AsO2-1 + H2O → AsO3-1 + 2H + 2e
*alkali medium = reducing agent trivalent form, acid medium = oxidizing agent
pentavalent form
22 | P a g e
4. Titanious ion → Titanic ion
Ti+3→ Ti+4 + e
5. Ferrous ion → Ferric ion
Fe+2 → Fe+3 + e
Example:
Oxalic acid, Ferrous sulfate, Sodium thiosulfate
Oxidizing Agents
Reactant containing a constituent atom or atoms which is converted to a lower state of

oxidation. A substance that causes the oxidation of some element or compd.
1. Permanganate ion → Manganous ion
MnO4-1 + 5e → Mn+2
2. Dichromate ion → Chromous ion
Cr2O7-2 + 6e → 2Cr+3
3. Bromate ion → Bromide ion
BrO-3 +6e → Br-1 in the presence of H2SO4
4. Ceric ion → Cerrous ion
Ce+4 + e → Ce+3
5. Iodine → Iodide ion
I2 + 2e → 2I
Example:
23 | P a g e
Potassium permanganate, Ceric sulfate, Bromine, Potassium iodate
Reduction Oxidation
Valence Decrease Valence Increase
Gain Electron/s Lose Electron/s
Reduction Oxidation
Oxidizing Agent Reducing Agent
Rules in REDOX reaction:
1. Oxidation state of an element in a free state of the uncombined form is = 0
2. Oxidation state of Hydrogen
= (+1) in compound
= (-1) with metals
3. Oxidation state of Oxygen
= (-2) in compound
= (-1) in peroxides
4. Oxidation state of:
Group 1A = (+1)
Group 2A = (+2)
Halogens = (-1) but = (+1) with Oxygen
Fluorine is always = (-1)
5. For monoatomic compounds the charge is its oxidation state
6. Algebraic sum of oxidation state of Neutral compound = 0
7. Polyatomic ions = Ionic charge
Types of titration in Oxidation – Reduction Method:
24 | P a g e
Permanganometry
STD.SOLN. Potassium permanganate
P.STD. Sodium oxalate
IND. None
END PT. Pink Color
SX. ANALYSED Hydrogen peroxide, Potassium bromide, Mallic Acid in Cherry juice, Potassium
nitrite, Sodium nitrite
- Can be standardized easily

- Can retain its conc. for long period of time
- The reaction of permanganate in solution is rapid
- Can serve as an indicator in titration
- Valuable and powerful oxidizing agent used for the titration of iron
Cerimetry
STD.SOLN. Ammonium Ceric Sulfate, FAS
P.STD. Arsenic trioxide
IND. Orthophenanthroline TS
END PT. Pale green = O.A.
Red = R.A.
SX. ANALYSED Iron containing compds, Menadione, Ascorbic acid
- Ceric sulfate is a powerful oxidizing agent comparable to that of permanganate with the
advantage that it can be used in titrations of organic substances
- Less susceptible to decomposition
- Can be used in the titration of ferrous ion in the presence of chloride at room temp.
- Ceric sulfate should not be boiled with HCl as reduction would take place
- Ceric sulfate should be conducted only in acid media to prevent hydrolysis
- Stable over a prolong periods even on boiling
- React quantitatively with oxalate or arsenic ion
- May be employed in the determination of reducing agent in the presence of high conc.
Of HCl
- Not too highly colored to obstruct vision when reading the meniscus
25 | P a g e
Iodimetry
STD.SOLN. Sodium thiosulfate Solutions, Iodine Solutions
P.STD. Potassium dichromate
IND. Starch TS, Carbon tetrachloride, Chloroform
END PT. Disappearance of Blue Color
SX. ANALYSED Reducing Agents, thiosulfates, Sulfites, Arsenites, Mercurous
- The free iodine solution is used in iodimetry titration

- The formation of free iodine solution is very difficult because iodine is less soluble in water
- So the solution of iodine is made with the use of potassium iodide
Iodometry
STD.SOLN. Iodine solutions
P.STD. Arsenic trioxide
IND. Starch TS
END PT. Appearance of Blue Color
SX. ANALYSED Oxidizing Agents, Fe, Cu, Mn, Cr, Co, Arsenous, Chlorine, Bromine, Iodine
- A process wherein a sample of an oxidizing agent is made to liberate an equivalent

amount of iodine
- Indirect reactions that involves iodide
- Never carried out in a strongly
REDOX Method using 0.1N Bromine
STD.SOLN. Bromine solution
P.STD. Substance to be assayed
SX. ANALYSED Aniline, Phenol, Resorcinol
- Also known as the Koppesschar’s solution

- Bromine is liberated when the solution is acidified
- Standard solution does not contain bromine but rather an equivalent amount of
potassium bromate and excess potassium bromide
26 | P a g e
REDOX Method with Potassium iodate
STD.SOLN. Potassium iodate solution
P.STD. Substance to be assayed
SX. ANALYSED Arsenites, Iodides, Reducing agents
Indicator Oxidized Reduced Form

Form
2,2 – Bipyridine (Ru Colorless Yellow
Complex)
Nitrophenanthroline
(Fe Complex) Cyan Red
N– Violet –
Phenylanthroline Red
Acid Colorless
1, 10 –
Phenanthroline (Fe Cyan
Complex)
Red
N–
Ethoxychrysoidine Red
2,2, - Bipyridine (Fe Cyan Yellow

Complex)
Red
GRAVIMETRIC ANALYSIS
Isolating constituent from the sample and determining its pure state and weighing it
accurately
It may be carried out by:
1. Precipitating the sought substance in an insoluble form
2. Depending on pure metal by electrolysis
3. Converting substance into a gas

27 | P a g e
* precipitation is by far the most widely used
Factor
Weigh of the constituent determined or sought and is equivalent to the unit weight of a
given substance
Formula:
𝑀.𝑊.𝑜𝑓 𝑠𝑥 𝑡𝑜 𝑏𝑒 𝑑𝑒𝑡𝑒𝑟𝑚𝑖𝑛𝑒𝑑
E= 𝑀.𝑊.𝑜𝑓 𝑝𝑝𝑡 𝑓𝑜𝑟𝑚𝑒𝑑
𝑊×𝐸
% = 𝑆
× 100
Where:
W = weight of precipitate involving the sx assayed
E = gravimetric factor
S = weight of sample
SPECIAL METHODS USED IN PHARMACEUTICAL ANALYSIS
ASH CONTENT
Total Ash
Residue remaining after incineration or ignition (incineration = natural drug, ignition =

chemical substance)
Acid Insoluble Ash
Part of total ash, insoluble in diluted HCl (residue = presence of silica)
Formula:
% Total Ash=
𝑤𝑡.𝑜𝑓 𝑐𝑟+𝑠𝑥 𝑎𝑓𝑡𝑒𝑟 𝑖𝑛𝑐𝑖𝑛𝑒𝑟𝑎𝑡𝑖𝑜𝑛−𝑤𝑡.𝑜𝑓 𝑐𝑟

𝑤𝑡.𝑜𝑓 𝑐𝑟+𝑠𝑥−𝑤𝑡.𝑜𝑓 𝑐𝑟,
× 100
28 | P a g e
% Acid Insoluble Ash=
𝑤𝑡.𝑜𝑓 𝑐𝑟+𝑠𝑥 𝑎𝑓𝑡𝑒𝑟 𝑖𝑛𝑐𝑖𝑛𝑒𝑟𝑎𝑡𝑖𝑜𝑛−𝑤𝑡.𝑜𝑓 𝑐𝑟

𝑤𝑡.𝑜𝑓 𝑐𝑟+𝑠𝑥−𝑤𝑡.𝑜𝑓 𝑐𝑟,
× 100
% Moisture Content =
𝑤𝑡.𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒−𝑤𝑡.𝑜𝑓 𝑑𝑟𝑖𝑒𝑑 𝑠𝑎𝑚𝑝𝑙𝑒

𝑤𝑡.𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
× 100
WATER CONTENT
Crystallized formed = hydrates included in the chemical formula
Determined for the following reasons:
1. Crude drugs are sold with a guaranteed assay for active constituent must calculate its moisture
free drug
2. Variable quantities adversely affect the calculated results
Methods used in Water content determination:
Gravimetric Method I
Containing constituents other than water volatile in 105℃
Formula:
𝑖𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑡.−𝑓𝑖𝑛𝑎𝑙 𝑤𝑡.

% Water Content = × 100
𝑖𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑡.
Gravimetric Method II
Containing ether soluble constituents volatile at 105℃
Example: Determination of water content of Acacia by gravimetric method
Azeotropic Method
29 | P a g e
Determination of many vegetable drug containing 2% or more of moisture.
50 – 100g are needed as sample
Toluene and Xylene are official solvent for this method
Example: Determination of moisture content of Digitalis by the Toluene Distillation
Formula:
𝑚𝐿 𝑜𝑓 𝑟𝑒𝑎𝑑𝑖𝑛𝑔.
% Water Content = 𝑚𝐿 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
× 100
Titrimetric Method / Karl Fischer Method
Most rapid require only small amount of sample, consists of iodine, sulfur dioxide,
pyridine and methanol
1mL of Karl Fischer reagent = 5mg of water
Sodium tartrate as primary standard and canary yellow is the endpoint
Formula:
0.1566×𝑊(𝑚𝑔)
F= 𝑉(𝑚𝐿)
𝑆×𝐹
% Water Content = 𝑊
× 100
Where:
S = volume of reagent used
F = water equivalence factor
W = weight of substance
Water Content = 𝑆 × 𝐹
Where:
S = volume of reagent used
30 | P a g e
F = water equivalence factor
Dew Point Method
Determined by noting the temperature at which a dew point/mist forms when the system
is suddenly cooled under adiabatic expansion
Electrolytic Hygrometric method
Amount of electric current is a measure of water content
EXTRACTIVES
A measure of the amount of certain constituents or group of related constituents which

the drug contains.
It is important that the solvent used will not dissolve the appreciable amount of
substances other than those sought in the extraction
Ether Soluble Volatile Extractives
- Determination of drugs containing volatile oils
Ether Soluble Non Volatile Extractives
- Determination of drugs containing active constituent associated with volatile matter
Alcohol Soluble Extractives
- Solvent used for resinous matter

- Frequently employed to determine approximately the amount of resin in those drugs in
which resinous matter is the important constituent
Hexane Soluble Extractives
- Good solvent for fats and fatty oils
Water Soluble Extractives
- Applied to drugs containing one or more important constituents which are soluble in
water
31 | P a g e
Formula:
% Extractive = wt of Residue
CRUDE FIBER EXTRACTIVES
A residue consisting chiefly of cellulose that remains undissolved after successive

treatment with boiling acid and alkali
Formula:
% Crude Fiber Extractives:
Permitted loss of some weight of official drugs are as follows:
Drugs % Permitted Loss

Calamine 2%
Magnesium sulfate 40 – 52%
Magnesium 20 – 27%
phosphate
Zinc oxide 1%
Calcium 8%
phosphate, Tribasic
Kaolin 15%
Magnesium 30 – 33%
hydroxide
Titanium oxide 0.5%
CONSTANTS OF FATS, FATTY OILS, WAXES, BALSAMS, RESINS, ETC.
Fixed Oils
32 | P a g e
Liquid glycerides (glyceryl oleate)
Fats
Solid glycerides (glyceryl stearate)
Waxes
Esters of high molecular weight of monohydric alcohol with high molecular weight of fatty
acids
Balsams
Substance with benzoic or cinnamic acid
Resins
Solid or semi solid extractives from plants
*the fats and oils to be employed in the determinations of their chemical constants should
undergo preliminary treatment if they are turbid due to separation of stearin
Preparation of sample of Fats and Oils:
ACID VALUE
- No. of mg of KOH to neutralize the free acids in one gram of complex composition
Example:
Determination of acid value of Rosin in terms of mg of KOH in one gram of sample
Determination of acid value of COD liver oil in terms of 0.1N NaOh in 2g of sample
Formula:
𝑁×𝑚𝐿×𝑚𝐸𝑞 𝑜𝑓 𝐾𝑂𝐻
AV = 𝑔 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
× 1000
SAPONIFICATION VALUE
33 | P a g e
- No. of mg KOH required to neutralize in one gram of sample composition
- HCl cannot be substituted with H2SO4 product will not dissolve
- Alcoholic KOH has more advantage than aqueous KOH
- Blank Test eliminate errors by absorption of CO2
Example:
Determination of saponification value of cottonseed oil
Formula:
(𝑚𝐿 𝑜𝑓 𝐻𝐶𝑙𝐵𝑇−𝑚𝐿 𝐻𝐶𝑙𝐴𝑇)×𝑁×𝑚𝐸𝑞𝑜𝑓 𝐾𝑂𝐻

SV = × 1000
𝑔 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
SV = EV + AV
ESTER VALUE
- No. of mg per g of KOH to saponify esters

- Important in the analysis of beeswax
- Serves to indicate presence of adulterants like paraffin
- Increase AV = Decreases EV, Decreases AV = Increases EV
Example: Direct determination of ester value
Formula:
EV = SV (w/o free acids)
EV = SV – AV
𝑚𝐿×𝑁×𝑚𝐸𝑞𝑜𝑓 𝐾𝑂𝐻
EV = 𝑔 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
× 1000
UNSAPONIFIABLE MATTER
- Determination of adulterants like phytosterols and cholesterols
Formula:
𝑤𝑡.𝑜𝑓 𝑟𝑒𝑠𝑖𝑑𝑢𝑒
% UM = × 100
IODINE VALUE
34 | P a g e
- Iodine flask
- Measure the proportion of unsaturated fats & fatty acids
- Degree of saturation of fatty acids
- No. of grams of iodine absorbed in 100g of complex substance
- Methods are HUBL, HANUS, WIJS
Example: Determination of Iodine Value of Olive oil
Formula:
(𝑚𝐿 𝑜𝑓 𝑁𝑎2𝑆2𝑂3𝐵𝑇−𝑚𝐿 𝑁𝑎2𝑆2𝑂3𝐴𝑇)×𝑁×𝑚𝐸𝑞𝑜𝑓 𝐼𝑜𝑑𝑖𝑛𝑒

IV= × 100
HYDROXYL VALUE
- No. of mg in 1 gram of complex substance

- Toluene serves as a mutual solvent for the solid cetyl alcohol = acetyl chloride + cetyl
acetate
- Pyridine acts as a condensing agent by reacting with hydrogen
Formula:
HV=
(𝑚𝐿 𝑜𝑓 𝑁𝑎𝑂𝐻𝐵𝑇 − 𝑚𝐿 𝑁𝑎𝑂𝐻𝐴𝑇) × 𝑁 × 𝑚𝐸𝑞𝑜𝑓 𝑁𝑎𝑂𝐻

× 1000
ACETYL VALUE
- Determined by acetylating hydroxyl fatty acids

- No. of g of acetyl in 1 gram of KOH
Formula:
𝑆𝑉−𝐴𝑉
AcV = 1−0.000755 × 𝑆𝑉
VOLATILE OILS
- Essential Oils
- Ethereal Oils
- Essences
35 | P a g e
Important chemical components of volatile oils:
Hydrocarbons
1. Monoterpene – 2-3 isoterpenes (C10H16)
2. Sesqueterpene – 3 or more isoterpenes (C15H24)
Examples: Camphene, Limonene, Bornylene, Fenchene, Dipentene, Sylvestrene, phellandrene
Alcohols
1. Acyclic – open structure
2. Monocyclic – 1 ring cycle
Examples: Linalool, Geraniol, Citroneol, Terpineol, Borneol, Menthol, Santalool
Aldehydes
- Good fragrance
- Good anti inflammatory activity
Examples: Benzaldehyde, Cinnamic aldehyde, Salicylic aldehyde, Citrol, Citronellal
Ketones
- Increase mucous secretion

- Toxic but used in tissue regeneration
Examples: Camphor, Carvore, Fenchone, Thujone, Menthone
Phenols
- Antiseptic, Antibacterial Disinfectant
Examples: Anethol, Eugenol, Carvacrol, Saffrol, Chavicol
Acids
Examples: Propionic, Butyric, Valeric, Benzoic, Cinnamic, Hydrocyanic Acids
Sulfur
Examples: Allyl isothiocyanate

36 | P a g e
Physical constants of volatile oils:
Specific Gravity
- 0.84 – 1.2
- Pycnometer, Mohr, Hydrometer, Westphal Balance
Oils lighter than Oils heavier than

Water Water
Orange, Caraway, Anise, Cinnamon,
Coriander, Lemon, Clove, Sassafras
Turpentine Oils
Rotatory Power
- Measured by Laurent half-shadow polarimeter

- Presence of adulterants is determined by its influence the rotatory power values.
Refractive Index
- Most commonly used instrument is the Abbe Refractometer
Congealing Point
- Increase CP = Increase V. Oils, Decrease CP = Decrease V. Oils
Distillation range or Limits
- Is determined by the general method described under Boiling and Distilling Ranges in the
USP.
Fractional Distillation
- It serves either to separate the various components of volatile oils or to detect

adulteration
Solubility
- Practically all the volatile oils exhibit almost constant solubility in 90, 80 or 70% alcohol.
Consequently, the test of the solubility of a volatile oil in diluted alcohol frequently gives
37 | P a g e
valuable data relative to its purity, since the common adulterants, are slightly soluble in
80 of 70% alcohol.
Factors causing deterioration of the volatile oils:
1. When exposed to light and air their fragrance is lost
2. Those containing terpenes produces peroxides
3. In long standing, volatile oils thicken and becomes resinified
4. Tin containers promote deterioration of odor and development of color
*isolation through steam distillation, special distillation method has been designed
*condenser, to avoid possible loss, provide direct reading of the volume of the oil
*oil lighter than water, directly measured in the receiver which is provided with lower portion
graduated cylinder
*oil heavier than water = Extraction with Clevenger apparatus
Determination of Components of Volatile oils:
DETERMINATION OF VOLATILE OIL IN SPIRITS
- Assay for volatile oil in spirits is based on the isolation of the oil from the other
components of the spirit by the use of an immiscible solvent and measuring the volume
of the liberated oil
Formula:
Steps:
1. mL of kerosene added divided by no. of divisions occupied by the volume of kerosene plus
0.01
2. no. of divisions occupied by the kerosene mixture minus the division of volume of kerosene
3. Answer in no.2 multiply by the answer in no. 1 = mL of Volatile Oil
4. Get the percent of volatile oil in spirit using the formula below?
𝑚𝐿 𝑜𝑓 𝑣𝑜𝑙𝑎𝑡𝑖𝑙𝑒 𝑜𝑖𝑙
% VO in S = × 100
𝑚𝐿 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
38 | P a g e
C1V1 = C2V2
DETERMINATION OF ESTER CONTENT
- Serves to detect adulteration and to establish quality of oils valued for their ester content
Formula:
% Total Esters =
(𝑚𝐿𝐵𝑇−𝑚𝐿𝐴𝑇)×𝑁×𝑚𝐸𝑞 𝑜𝑓 𝑒𝑠𝑡𝑒𝑟
× 100
DETERMINATION OF ALCOHOL CONTENT
- Alcohol content is so valuable that it is alone can be a sufficient to prove the purity and
value of the volatile oil
- Consist of the conversion of the free alcohol to its acetate ester and saponification of the
freshly produced acetate and original acetate with standard alcoholic potassium
hydroxide
Formula:
% Total Menthol =
𝐴×7.813
𝐵−(𝐴×0.021)
× (1 − (𝐸 × 0.0021))
Where:
A = is the difference between the mL of titrant used in the blank and actual test
B = M.W. of acetylated oil – M.W. of menthol
E = % of esters as acetylated oil
*this formula could change depending on what alcohol content is to be assay
*explanation of the components of the formula are as follows:
39 | P a g e
% Total Alcohol =
𝐴×7.813
× (1 − (𝐸 × 0.0021))
𝐵−(𝐴×0.021)
DETERMINATION OF ALDEHYDE CONTENT
- When no other constituents are present which will react with the reagent, the assay of
aldehydes may be performed using Bisulfite Method, cassia flask is used for this assay
- The bisulfite addition product dissolves in water, leaving the non-aldehyde constituents
as a water-insoluble layer. The volume of this water insoluble layer is then measured in a
cassia flask
- The portion of the oil that does not react to form a water – insoluble addition product
rises to the surface, and when the flask is filled, this oily layer rises into the graduated
neck of the cassia flask, where its volume can be measured. The volume of the residual
oily layer subtracted from the volume of the sample of oil used represents the volume of
the aldehyde constituents that formed a water- soluble addition product with the
bisulfite.
- Volatile oils containing small amount of aldehydes cannot be assayed accurately by this
method.
Formula:
Bisulfite Addition Reaction Method
% Total Aldehyde =
𝑉 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 − 𝑉 𝑜𝑓 𝑟𝑒𝑠. 𝑙𝑖𝑞𝑢𝑖𝑑

× 100
𝑉 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒
40 | P a g e
Hydroxylamine Method
% Total Aldehyde =
(𝑚𝐿𝑁𝑎𝑂𝐻𝐵𝑇 − 𝑚𝐿𝑁𝑎𝑂𝐻𝐴𝑇) × 𝑁 × 𝑚𝐸𝑞 𝑜𝑓 𝑎𝑙𝑑𝑒ℎ𝑦𝑑𝑒

× 100
DETERMINATION OF PHENOL CONTENT
- Volatile oils that contain phenols when shaken with solutions of sodium hydroxide
diminish in volume because of ready solubility of the phenol constituents in alkali; the
non phenolic portion of the oil remains undissolved.
Formula:
% Total Phenol =

× 100
DETERMINATION OF KETONE CONTENT
- Only two of the official volatile oils are assayed for their ketone content. (Caraway oil &
Spearmint Oil)
- Method of determination of ketone in these two volatile oils are the Bisulfite Addition
Reaction Method and Hydroxylamine Method
- NLT 55% is required for the carvone content of these two volatile oils
Formula:
% Total Ketone =

× 100
Hydroxylamine Method
% Total Ketone =
(𝑚𝐿𝑁𝑎𝑂𝐻𝐵𝑇−𝑚𝐿𝑁𝑎𝑂𝐻𝐴𝑇)×𝑁×𝑚𝐸𝑞 𝑜𝑓 𝑎𝑙𝑑𝑒ℎ𝑦𝑑𝑒
× 100`
41 | P a g e
ALKALOIDS & AMINE DRUGS
May be defined as chemical substances which:
1. Obtained from plant, animal, or synthetic sources
2. Contain organic Nitrogen within their chemical structure
3. Usually possesses physiological activity
Physical properties:
Solubility
1. Alkaloids R3N (sometimes called free alkaloids) are sparingly soluble in water but readily soluble
in most organic solvents immiscible in water such as ether, chloroform, carbon tetrachloride
2. Alkaloids salts (R3 NH+1 Cl-1) readily soluble in water and sparingly soluble in immiscible solvents
Chemical Properties:
Reactions in Acids and Bases
1. Alkaloids combine directly with acids to form salts that are usually soluble in water but insoluble
in certain organic solvents
Example:
R3N + HCl → R3N NH+1 Cl-1
Water soluble
2. Alkaloids are liberated from aqueous solutions of their salts by alkali
Example:
R3NH+1 Cl-1 + NaOH → R3N + NaCl + H2O
Soluble in organic solvent
3. Alkaloids form highly insoluble precipitates with considerable no. of reagents, especially with
salts of some heavy metals such as mercury, gold and platinum
42 | P a g e
The methods employed to separate alkaloids from other constituents involve the use of
immiscible solvents such as water in ether, with ether chloroform mixture. The process is carried
out as follows:
1. An accurately weighed portion of the drug is treated with a suitable alkali
2. An organic solvent such as ether is then added which dissolves the free alkaloids, the separation
of the immiscible solvents is accomplished by means of separatory funnel
3. An aliquot portion or all ethereal solution with definite weight of sample taken is separated and
shaken with several portions of acidulated water.
4. Completion of extraction is determined by testing a portion of the latter with a suitable

alkaloidal reagent.
5. The alkaloidal salts formed with the acid dissolve in water
6. The acid extractions obtained are combined made alkaline and shaken with successive portions
of other
7. The alkaloids liberated from their salts by the alkali pass into solution in ether leaving water
soluble impurities behind
8. The separated ethereal extractives may then be combined, evaporated, to dryness and weigh
9. The residual alkaloid may be dissolved in an excessive of acid of known normality and the excess
of acid determined by titration with a standard solution of alkali using a suitable indicator to show
when the endpoint is reached
10. In alkaloid assays by volumetric methods, the use of methyl red solution is recommend in all
the titrations
Alkaloid Test solutions:
Mercuric Iodide TS
Known as Valier’s Reagent is prepared by slowly adding 10% solution of Potassium iodide
to red Mercuric iodide until almost all the red Mercuric iodide is dissolved. The excess Mercuric
iodide is then removed by filtration. This reagent forms a white precipitate
Iodine TS
43 | P a g e
Known as Wagner’s Reagent is a solution containing iodine and Potassium iodide
dissolved in distilled water. A 0.1N iodine solution may be employed. This solution yields a reddish
or brown precipitate
Mercuric potassium iodide
Mayer’s reagent is a solution of 1.358g of mercuric chloride in 60mLof water with 5g of KI

in 10mL of water and the mixture diluted to 100mL. This reagent gives white or slightly yellow
precipitates with dilute solution of alkaloids
Examples: Assay of Belladonna Leaf,
Formula:
𝑥
Cacid = 𝑚𝐿 𝑜𝑓 𝑎𝑐𝑖𝑑 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
1−𝑥
Cether =
𝑚𝐿 𝑜𝑓 𝑒𝑡ℎ𝑒𝑟 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
𝑥/𝑎𝑐𝑖𝑑 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
K=
(1−𝑥)/𝑒𝑡ℎ𝑒𝑟 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
𝑚𝐿 𝑜𝑓 𝑒𝑡ℎ𝑒𝑟
W=
𝐾×(𝑚𝐿 𝑜𝑓 𝑎𝑐𝑖𝑑+𝑚𝐿 𝑜𝑓 𝑒𝑡ℎ𝑒𝑟)
*the following equation is useful in determining the quantity of solute remaining after n
extractions
𝑉1
Wn = 𝑊( )𝑛
𝐾×𝑉2+𝑉1
Where:
K = C2/C1
C2 = conc. Of solute in the extracting solvent
C1 = conc. Of solute in the original solvent
W = weight of solute originally taken
Wn = weight of solute remaining in the original solvent after n extractions
V1,V2 = volume of solvents 2 & 1 respectively
n = no. of extractions
44 | P a g e
QUALITY CONTROL 2
45 | P a g e
STATISTICAL QUALITY CONTROL
- Is the monitoring quality by the application of statistical methods in all stages of

production.
CONTROL CHARTS
- A tool which may influence decisions related to the functions of applications, production
and inspection
There are two basic quality control charts which are based on the measurability of the
quality characteristics namely:
Attribute Chart
- A chart which makes use of discrete data classifying the number of items conforming
and the number of items failing to conform ta ant specifications
- One example is the control chart for fraction defective known as P-Chart
46 | P a g e
Variable Chart
- A chart using actual records of numeric measurement on a full continuous scale such as
meter, gram, liter.
- Examples are:
47 | P a g e
48 | P a g e
49 | P a g e
50 | P a g e
51 | P a g e
52 | P a g e
53 | P a g e
54 | P a g e
55 | P a g e
56 | P a g e
57 | P a g e
58 | P a g e
59 | P a g e
60 | P a g e
61 | P a g e
62 | P a g e
63 | P a g e

Quality Control &amp; Assurance With Instrumentation

Hochgeladen von

Dokumentinformationen

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Quality Control &amp; Assurance With Instrumentation

Hochgeladen von

Copyright:

Verfügbare Formate

QUALITY CONTROL 1

JENKINS’ QUANTITATIVE PHARMACEUTICAL

Quality control guarantees within reasonable limits that a product is:

1. Free from impurities

2. Physically and chemically stable

3. Contains the amount of active ingredients stated on the label

4. Provides optimal release of a.i. when the product is administered.

Approved sources of guidelines for drug quality required by certain practitioners or

4. Packaging and storage

7. Corresponding tests for chemical and physical constants

Source and Nature of Errors

They arises from causes such as:

1. Personal errors made by the individual analyst.

2. Errors of method caused by faulty procedure.

3. Apparatus errors due to poor construction or calibration

Accuracy and Precision

Is used to denote the agreement of an experimental result of a series of experimental

Difference between the mean and the true value.

Found by dividing the absolute error by the true error.

Relative Ave. Dev.

Found by dividing the average deviation by the mean.

Relative Std. Dev.

Found by dividing the average deviation by the mean X 100.

Defined as all certain digits of measurement plus one doubtful digit.

Rules of Significant Figures:

1. All non zero are significant.

2. Zeros between non-zero digits are significant

Act of drawing out samples from a given batch of materials or product.

4. As an alternative to withdrawing of official samples according to the methods 1, 2, 3 the official

Square Root System

Military Standard Table

Process of determining the potency, strength or percentage purity of a drug preparation.

Process of determining the elements or compounds present in the given sample.

METHODS OF ANALYSIS IN QUANTITIVE PHARMACEUTICAL CHEMISTRY

A.K.A Titrimetric Analysis Determination of the volume of a solution of known

Chemical substance being analysed

Substance of known purity and use to standardize solution.

Requirements for primary standard:

1. Must be easy to prepare and pure

2. Must be definite known composition

4. Must react stoichiometrically with the substance present in the solution

5. Must be soluble in water

Primary standards for acids:

1. Anhydrous sodium carbonate

Primary standards for alkalis:

Accomplished by the use of another standard solution.

Solution of known concentration

Solution of known concentration.

Determination of the concentration of a standard solution.

Gram-equivalent weight (GEW)

Defined as weight in grams which is chemically equivalent to 1 gram-atom of hydrogen.

In neutralization reactions it is defined as weight of a substance in grams which contains,

Gram-milliequivalent weight (GmEW)

Defined as the number of gram equivalents involved in a quantitative procedure.

Defined as the number of gram milliequivalents involved in a quantitative procedure.

Is the strength in grams per mL of solution or the weight of a substance chemically

Concentration of a Standard Solution can be expressed in terms of:

Concentration expressed as number of equivalents of solute per liter or milliequivalent

Concentration of solution in terms of moles per liter.

Contains a mole in one thousand grams of solution

Indicator pH Range Acid Base

Malachite green 0.0-2.0 Y G

Methyl yellow 2.9-4.0 R Y

Methyl orange 3.2-4.4 P Y

Quality Control & Assurance With Instrumentation

Quality Control & Assurance With Instrumentation