PHCA 201 ☆ Competency Enhancement & Evaluation 1
Pharmaceutical Analysis 1 ☆ DOM 2
Lecturer: pacquiao, ian ace
Summer ☆ S.Y. 2021-2022
Quality Control Defined:
● Application of the procedures of qualitative and
quantitative analytical chemistry
- To the analysis and determination of the purity
and quality ofdrugs and chemicals used in
pharmacy
- To the analysis of the chemical constituents
found in the human body whose altered
concentrations during disease states serve as
diagnostic aids
- To the analysis of medicinal agents and their
metabolites found in biological systems
Therefore, QC has value in ...
Guarantees of Quality Control
● QC procedures can give the assurance that a product
possesses the following characteristics:
- is free of impurities
- is physically and chemically stable
- contains the amount of active ingredients as
stated in the label
- provides optimal release of active ingredients
when the product is administered
Introduction to Pharmaceutical Analysis
Quality
● Sum of all factors which contribute directly or indirectly to
the safety, effectiveness, and reliability of the product
● Ensures that drug products are designed and produced to
meet or exceed customer requirements for efficacy and
safety
Quality Management System
- A coordinated set of activities that directs and controls an
organization with regard to quality
Quality Control
- Application of quantitative and qualitative pharmaceutical
chemistry to the analysis of:
○ Purity and quality of drugs and chemical
constituents
○ Diagnostic testing for chemicals found in the
body in altered concentrations
○ Analysis of medicinal agents and metabolites
in biological systems
- Considered as Process control
- Monitors activities related to analytical examination of
testing
- Goals
○ Detect, evaluate and correct errors due to
system failure, environmental conditions and
operational performance
- Guarantees of QC in relation to products:
○ Product is free of impurities
○ Product is physically and chemically stable
○ Product contains the amount of active
ingredients as stated in the label
Pharm. Analysis 1 CEE ☆ 01.
▪ Therapeutic failure - if active
ingredient is not released
○ Product provides optimal release of active
ingredients when the product is administered
- Types of QC processes
○ Quantitative examinations
● Measured as a numerical
value
● Assays
○ Qualitative examinations
● Measures presence or
absence of a substance
● Color
○ Semi-qualitative examinations
● Values are an estimate of
measured analyte, usually
in a range or a scale
● Benedict’s test
○ Staff of QC operations
▪ Are responsible for sampling, analytical testing of raw
materials, packaging components and labeling
materials
▪ Conducts monitoring of parameters like in-process
testing, environmental monitoring, operations
compliance and release tests on dosage forms
QC - day to day tasks and testings
QA - documentation
If it is not documented, it did not happen
Quality Assurance
- part of quality management focused on providing
confidence that quality requirements will be fulfilled
- defined as planned and systematic activities that can
demonstrate a product’s capacity to fulfill requirements for
quality
- Department that is responsible for quality policies are
adopted, identification and preparation of policies and
standard operating procedures and determines product
meets applicable specifications set by internal standards
and good manufacturing practices
- Functions:
○ Quality monitoring, audit function
Basic Principles of Pharmaceutical Analysis
Definition of Important Terms:
1. Specification- a document that contains a list of tests,
references to analytical procedures and appropriate
acceptance criteria
a. Categories include: intended use of a product,
acceptance criteria for release testing & stability
testing
2. Compendia – a collection of data gathered and presented
in the form of a book. Examples include: USP/NF, BP,
EuPharm
3. Monograph - A written standard that describes an article
like a drug substance, drug product, excipients or
compounded preparation
a. Contents include: name of substance, definition,
packaging requirements, storage requirements,
labelling requirements, information on tests to
ensure identity, strength, safety, quality and purity
b. Guarantees include the provision of a public
standard consumed in a global marketplace
4. Universal Tests – are conducted to all drug products it
includes:
a. Description: appearance testing
b. Identification: verification of identity (qualitative)
 c. Assay: quantitative measure of compound in a 2. Performing a parallel control determination
sample 3. Blank determination
d. Impurities: threshold presence of 4. Cross-checking of results with different methods of
related/degradation substances in the drug sample analysis
5. Method of standard addition
Analytical Method Validation 6. Method of internal standards
- To make sure procedures are done correctly
Pharmaceutical Analysis
Reasons for Analytical Method Validation: Important Terms to remember:
1. Regulatory Requirements 1. Titration – method of analysis that determines the
2. Proper practice of Good Science precise endpoint of the reaction = identifying the
3. Quality Control Requirements set by FDA precise quantity of reactant in the titration flask
Process of Analytical method Validation includes:
1. Planning and deciding on the method validation 2. Analyte – compound meant to be assayed/analyzed
experiments 3. Titrant / Standard solution – solution of known
2. Writing and approval of method validation protocol concentration used for analysis
3. Analysis of the method validation data
4. Reporting the analytical method validation 4. Indicator – solution/compound that allow the endpoint
5. Finalizing the analytical method procedure to manifest in a titration process
Content Of a Validation Protocol Includes: 5. Equivalence point/Stoichiometric Point – point at which
1. Objective of the protocol titrant is chemically equivalent to the analyte
2. Validation parameters that will be evaluated
3. Acceptance criteria for all validation parameters 6. Endpoint – an observable physical change in the
evaluated titration process indicating the reach of the equivalence
4. Details of the experiments to be performed point
5. Draft analytical procedure
7. Primary Standard - a highly purified compound that is
used as a reference standard in titration processes
Information that should be included in the final analytical
(high purity, stable in air, independent of humidity,
procedure includes:
readily available, reasonably soluble, large formula
1. Rationale of the analytical procedure and description of
weight); solid
the capability of the method
2. Proposed analytical procedure 8. Secondary Standard - a standard used that does not
3. List of permitted impurities and its levels in an impurity meet requirements for a primary standard but is
assay available with sufficient purity and properties to be
4. Validation data acceptable as such (should be standardized using a
primary standard, stable and reacts completely and
Validation Characteristics include: rapidly with analyte; liquid, placed/used in burette or
1. Accuracy – closeness of values obtained from true erlenmeyer flask
value (trueness)
9. Standardization - This is a process where the
concentration of a solution is determined
10. Direct titration – a process where the titrant is added to
the analyte until a reaction goes to.
11. Back titration (residual) - where completion excess
2. Precision includes three parameters reagent is added to the analyte, and then the
Operating Time excess of this added reagent is determined.
Parameter Analyst Equipment Usually performed when an analyte reacts slowly with
Conditions Interval
Repeatability Same Same Short same the titrant in direct titration processes
Intermediate 12. Indirect Titration - a process where a substance is
Different Same Different Same
Precision reacted with the analyte and liberates a compound that
Reproducibility Different Different Different different can be determined by titrimetric methods
* Repeatability - 1 person, multiple trials
* Intermediate Precision - 2 people, same procedure, different
time frames Titrimetric Methods: Neutralization Reactions (Aciddimetry
* Reproducibility - different labs, different people and Alkalimetry) Acid-Base Titrations
Acidimetry – involves the analysis of inorganic and organic
3. Quantification limits lowest amount of the analyte in the alkaline/basic substances using an acid
sample that can be quantified (usually impurities and
Alkalimetry – involves the analysis of acidic substances using a
degradation products)
basic solution
4. Linearity - ability of an analytical procedure to obtain
test results of variable data which are directly Acid + Base → Salt + H2O
proportional to the concentration in the sample
5. Range – interval between the upper and lower Important things to remember in alkalimetric titrations:
concentration of the analyte in the sample 1. The normality of the solution obtained by dissolving the
acidic substance must be approximately the same as
6. Robustness – measure of the method to remain
that of the titrant.
unaffected by small but deliberate variations in method
2. The liquid acidic substance to be titrated must be
parameters during normal usage
brought to room temperature (25°C) before titration,
because many indicators offer different values at
Control of Quality in Analytical Methods
different temperatures
Error – defined as the difference in the numerical values
3. The quantity of acid to be taken should be calculated in
between a measured value and the true value, Types of errors
such a manner that approximately 30 to 40 ml of the
include:
previously standardized base shall be utilized for the
1. Determinate Errors – errors that have a definite value
assay.
and reasonable cause
2. Indeterminate Errors – cannot be pinpointed and are
Criteria for Indicators in Acid Base Titrations
random in nature
1. Can produce a sharp contrast between two colors
Minimization of Errors can be done by:
which it exhibits in acid and alkaline mediums
1. Calibration of Instruments

Pharm. Analysis 1 CEE ☆ 2

 2. The change in color will take place over a very small
range of pH values.
Rules for Use of indicators in Acid-Base Titrations
1. 3 drops of indicator should be used unless directed
2. Strong acid + strong base = phenolphthalein, methyl
red or methyl orange
3. Weak base + strong acid = phenolphthalein
4. Strong acid + weak base = methyl red
Titrimetric Methods: Non–Aqueous Titrations
This involves the titration of weak acids and bases using
non-aqueous titrants. Temperature should be monitored in
titration process due to high coefficient of expansion of solvents
used; Common factor is 1
Advantages of Non-aqueous titrimetry
1. Elimination of poor solubility of analytes
2. Enhancement of weak reactivity of certain analytes
3. Selectivity of titrations using a suitable solvent
4. Maintenance of speed, precision, accuracy and
simplicity comparable with classical methods of
analysis
Rules to observe in non-aqeous titrations:
1. Moisture and carbon dioxide should be avoided using
non aqueous procedures.
2. Moisture should be held to less than 0.05%.
3. Standardization & titration should be carried out as far
as possible at the same temperature because of high
coefficients of expansion common among organic
solvents.
Solvent types used in non-aqueous titrations:
1. Protophilic Solvents – basic in nature and react with
acids to form solvated protons
2. Protogenic Solvents – acidic in nature and promotes a
leveling effect on bases
3. Aprotic Solvents – chemically inert substances and
neutral in nature
4. Amphiprotic Solvents – solvents that possess both
protogenic and protophilic properties
Titrimetric Methods: Precipitation Methods
Titrations involved here are limited to use of silver as titrant to
analytes containing halogens and thicyanate. Due to the nature
of the process, a colored solution is necessary as an endpoint.
Limitations include:
1. Co-precipitation effects do not give a real composition
of the precipitate, and
2. Choice of appropriate indicator is very much limited.
Parameters for a good precipitation analysis
1. Precipitate formed must be insoluble,
2. Precipitation process should be fast and rapid,
3. Co-precipitation effects must be minimal, and
4. Detection of equivalence point must be apparently
visible.
Titration methods:
● Mohr’s Method (Direct) – determination of chlorides
using silver nitrate; indicator: Potassium Chromate =
red coloration; Used factor is 1
● Volhard’s Method (Residual) – it uses ammonium
thiocyanate to determine concentration of chlorides in
a solution using nitric acid; indicator: Ferric Ammonium
Sulfate = red coloration; Used factor is 2
● Fajan’s Method (Direct/Residual) – adsorption method
using adsorption dyes, change in color marks the
endpoint; indicators: dischorofluorescien, eosin y,
tetrabromophenolphthalein ethyl ester; Used factor is 1
Titrimetric Methods: Complexation Methods
Complexation Methods are based on complex formation
between the analyte and titrant and is used for titration of
polyvalent metal ions using EDTA as titrant; No factor
Pharm. Analysis 1 CEE ☆
Terms to remember in Compleximetric Titrations:
1. Complex – formed by the combination of a metal ion
with a molecule capable of donating electrons
2. Chelate – complex formed between a polyvalent metal
ion with a molecule that can donate electrons
3. Ligand – molecule that affords groups for attachment to
metal ions
4. Masking agent – used in covering metal ions that are
not meant to be analyzed in compleximetric titrations;
should act by precipitation, should form complexes that
are more stable than the interfering metal ion and color
formed should not obscure the endpoint
Things to remember in compleximetric titrations:
1. pH should be adjusted to stabilize complexes and to
achieve distinct color changes to the titration process
2. temperature should be controlled in order to stabilize
the complex formed, giving accurate data for
calculations
3. the disodium salt of EDTA is used due to increased
solubility in water
Titrimetric Methods: Redox Titration Methods
In this titration method, changes in the net electron charge of
the compound is the measure for reactions in titration processes
Assay Methods include:
1. Permanganate methods – use of potassium
permanganate in the analysis of pharmaceutical
substances; titration procedures are self-indicating;
KMnO4 should not come in contact with carbon related
products (cellulose, paper and etc.) to avoid
unnecessary oxidation
2. Indirect titration methods – compounds are converted
to an equivalent of oxalate salt before they can be
oxidized by potassium permanganate; example: Assay
of malic acid in cherry juice
3. Residual Titration Methods – has two categories:
a. [Standard Oxalic acid + analyte] = excess
oxalic acid is titrated with KMnO4
b. [Standard KMnO4 + analyte] = excess
KMnO4 is either: titrated using standardized
oxalic acid or use of ferrous ammonium
sulphate and then back titrated with more
standard KMnO4
4. Dichromate Titration Methods – more stable in
aqueous solution compared to KMnO4 but lacks
self-indicating ability as that of KMnO4
5. Ceric Sulfate Titration Methods – reduction method
applied when analytes require boiling for complete
reaction
Titrimetric Methods: Potentiometric Methods
Potentiometric titrations require the use of electrochemical cells
that generate electrode potential to determine the ionic species
in a solution. It covers all reactions discussed above. Its
advantage over other methods is that measurements can be
done in colored solutions whereas its disadvantage is that
readings take time to stabilize. Automatic potentiometers are
also used in the industry to avoid the hassle of use in titrimetric
methods.
Summary of Titrimetric Methods
Titration Type Direct Residual Indirect
Acidimetry √ √
Alkalimetry √ √
Precipitation √ √
Complexation √ √
Redox √ √ √
Iodimetry √ √
Iodometry √ √
Gclassroom:
https://classroom.google.com/u/0/c/NTM2ODIxNzcxNjkw
Video Lecture:
https://drive.google.com/file/d/113lS9T07AsKL1eT6fYLEH3v0
n8vzaxYh/view
3
PHARM ANALYSIS CALCULATIONS

Provide the following: A) Given B) Formula C) Calculations and D) Answer.

BOX YOUR FINAL ANSWERS!
1. The analyst was standardizing an sample of silver nitrate using CaCO3 as the primary standard. In the titration process, the
analyst use 300 mg of CaCO3 and consumed a total amount of 21 mL of silver nitrate with an unknown normality. Calculate
the normality of the silver nitrate solution

2. A 0.21 g sample of NaCl was assayed using Volhard Method, using 60 mL of 0.0988 N AgNO 3 and 15.1 mL of 0.1332 N
NH4SCN. Calculate the % NaCl in the sample.

3. What is the percentage of calcium in fruits using 10 g sample consuming 35 mL of 0.0214 M EDTA? Each mL of 0.05 M
EDTA is equivalent to 2.002 mg of Calcium

4. A 200 mg sample of 84% calcium carbonate was acidified and dissolved in 500 mL of solution. A 50 mL sample required
25 mL of an EDTA solution for titration. Find the molarity of the EDTA solution

5. Quality control protocols inside a factory making Sodium Hypochlorite Solution (Alrox TM ) were conducting their routine
quality control analysis for their newly-manufactured products. The head analyst was entasked to assay the sodium
hypochlorite content of the said batch made. After random sampling, the analyst was able to get 3mL from batch no.
22111324, added 2 grams of Potassium Ioodide, 10mL glacial acetic acid and 3 mL of starch solution and managed to
titrate it to completion with the use of 30mL of 0.2100 N sodium thiosulfate.
a. Calculate the % NaClO content in the sample obtained by the analyst
b. Does the sample conform to USP standard of NaClO content in this brand? Explain

6. Student IAP wanted to standardize a solution of iodine made by his laboratory partner. After weighing 0.2 grams of Arsenic
Trioxide (As2O3), and subjecting the sample to the titration process, he found out that the sample needed 43 mL of the
iodine solution. Calculate the normality of the iodine solution student IAP standardized

7. Sam Peterson, owner of Peter pharmaceuticals received insider information about certain factory worker stealing reagent
grade ascorbic acid (C6H8O6) and replacing it with starch during their formulation process. Worried about retaining the
quality of their products, Mr. Peterson hired a third-party analyst in order to assay the vitamin C samples which were
thought to be adulterated by the factory worker. Upon assaying, the analyst was able to use 47 mL of 0.3100 N iodine
solution on a 0.5 gram sample.
a. Calculate the % Ascorbic acid in the sample obtained by the analyst
b. If you were in the situation of Mr. Peterson, would you investigate further in this matter? Explain

8. A 5 mL sample of hydrogen peroxide solution required 15.6 mL of a permanganate solution in titration. In each mL of the
Permanganate solution is equivalent to 0.009845 g of Fe.
a. Calculate the normality of the permanganate solution
b. Calculate the % w/v of the Hydrogen peroxide that is present in the sample

9. Ten sodium salicylate (C 7 H 5 NaO 3 ) tablets labelled 500mg were dispersed in sufficient water to make 200mL. A 20mL
aliquot of the filtrate was titrated to a bromophenol blue endpoint in the usual way by 24.5 mL of 0.1200 N HCl. Calculate
the amount of a) the amount of sodium salicylate in each tablet and b) percentage of the labelled amount

10. If 30mL of sodium hydroxide solution required 45mL of a sulfuric acid in a titration, and 20mL of the sulfuric acid solution
were required in the titration of 0.4501g of pure sodium carbonate (Na 2 CO 3 ). What is the normality of the sodium
hydroxide solution?

11. If a 2.2250g sample of Zinc Oxide 92% ZnO, was treated with 53mL of 1.1011 N Sulfuric acid in the usual way, what
volume of 0.8988 N sodium hydroxide would be required in the back titration

Pharm. Analysis 1 CEE ☆ 4