Notes

1. 1
Introduction to Pharmaceutical
Analysis
By: Jafer S. (B.Pharm, MSc,
MPH, Assistant professor)

2. Learning Objectives
• At the end of this session , the student is expected to be able to :
 Understand the concept of the pharmaceutical analysis
 Discuss scope of pharmaceutical analysis
 Describe different aspects of quality control and quality assurance
 Describe official Methods of Standardization
 Describe steps in atypical quantitative analysis
 Discuss methods of quantitative Analysis
 Describe an analytical errors and their control
 Discuss validation of analytical methods
2

3. 3
Definitions
Analysis: A process that provides chemical or physical information
about the constituents in the sample or the sample itself.
Pharmaceutical analysis:
is a science which deals with identification and quantification
of drugs in raw materials, dosage forms and biological fluids.
Or
An applied science that insures the safety, efficacy and
stability of pharmaceutical products by using physical,
chemical, biological, pharmacological and
biopharmaceutical methods.
And it is also a technique that is used in elucidation of drug
entities from natural products.

4. Pharmaceutical analysis cont...
 What to test? the drug product
 Why to test? ensures the safety, efficacy and quality of
pharmaceutical products
 How to test? compendial and non-compendial methods presented in
regulatory documents
4

5. ©Gary Christian, Analytical Chemistry, 6th Ed. (Wiley)
Qualitative analysis is what.
Quantitative analysis is how much.

6. 6
Why analyzing drugs?
– It is one way (and often the only way) to judge
quality.
– Any hazards associated with the drug can be
ascertained and the necessary correction made
before marketing

7. 7
 Qualitative Analysis (identification) provides information
about the identity of species or functional groups in the
sample (an analyte can be identified).
 Quantitative Analysis provides numerical information of
analyte (quantitate the exact amount or concentration).

8. 8
Generally, pharmaceutical analysis procedures may be used
to answer any of the following questions:
1. Is the identity of the drug in the formulated product
correct?
2. What is the percentage of the stated content of a drug
present in a formulation?
3. Does this formulation contain solely the active
ingredient or are additional impurities present?
4. What is the stability of a drug in the formulation and
hence the shelf–life of the product?
5. At what rate is the drug released from its formulation
so that it can be absorbed by the body.

9. 9
6. Do the identity and purity of a pure drug substance to be
used in the preparation of a formulation meet specification?
7. Do the identity and purity of excipients to be used in the
preparation of a formulation meet specification?
8. What are the concentrations of specified impurities in the
pure drug substance?
9. What is the concentration of the drug in a sample of tissue
or biological fluid?
10. What are the Pka value (s), partition coefficients,
solubilities, and stability of a drug substance under
development?

10. 10
Scope of pharmaceutical analysis:
 Pharmaceutical industry
– Raw material control
– In-process control
– Dosage form control
 Government drug control laboratory (regulatory
agencies) …FMHACA

11. 11
Pharmaceutical research labs
 Advanced research
• Development of analytical method
• Process development
– Dosage form evaluation
– Stability studies
 Basic research
• Separation
• Identification
• Quantization
• Medicinal characterization

12. Introduction to quality control and quality assurance
12
What is Quality?
ISO definition:
"The totality of features and characteristics of a product or
service that bear on its ability to satisfy stated or implied
needs".
When projected on analytical work, quality can be defined as
"delivery of reliable information within an agreed span of time
under agreed conditions, at agreed costs, and with
necessary aftercare".

13. Quality Assurance
"the assembly of all planned and systematic actions necessary to
provide adequate confidence that a product, process, or service will
satisfy given quality requirements."
.
Quality Control:
A major part of the quality assurance
"the operational techniques and activities that are used to satisfy
quality requirements.
Quality of drugs should meet the standards related to safety,
potency, and efficacy.
- evaluated by various quality control methods.
13

14. 14
 A QC program for drug industry involves with
– batch-to-batch uniformity of a product
 QC is concerned with
 Sampling,
 specification and testing
 documentation and release procedures
Aim of QC
To evaluate whether the sample of drug complies with the
appropriate specifications, based on various tests
Types of tests for QC
– Physico-chemical methods
– Biological methods

15. 15
Objectives of Quality Control:
Make sure that
 proper sampling and analytical test are done
 products are made which demonstrate that all the
required sampling, inspecting and testing
procedures were actually carried out.
 the finished products contain active ingredients and
enclosed within their proper container and
correctly labeled.
–

16. 16
Objectives of Quality Control…
• Make sure that
– no batch of product is released to sale of supply
prior to certification by qualified person.
– sufficient reference sample of starting materials
and products are retained to permit future
examination of the product if necessary.

17. Official Methods of Standardization
17
 Official methods of standardization i.e. monographs of
pharmaceutical chemicals and formulated products are
descriptive
informative
Contain limits of purity,
standards of the product and
storage conditions.


18. 18
Monograph:
 A written description of the principal features of the substance
and the ways these features can be determined.
Pharmacopoeia:
 Monographs of pharmaceutical substances when collected
together.
 Pharmacopoeias are official documents that provide guidelines,
specifications, and analytical procedures for various drug
substances.
 A book containing the official standards for drug quality,
 Published by the authority of a government or a medical or
pharmaceutical society.

19. 19
 Quality of pharmaceuticals is based on pharmacopoeia
specifications.
 Drug manufacturers must comply with these pharmacopoeias
according to the regulations of different countries.
 The pharmacopeia of today is a quality standard for the
pharmaceutical industry and contains monographs, procedures
for general tests and assays, and a section on reagents and
solutions for drug substances, drug products, nutritional
supplements, and excipients.

20. 20
 The most referenced pharmacopeias are the British
Pharmacopoeia (BP), the European Pharmacopoeia (EP), the
Japanese Pharmacopoeia (JP), and the United States
Pharmacopeia (USP).

21.  “Pharmacopoeia” means a legal enforceable document issued or
accepted by the government containing
 the particulars of medical drug preparation,
 physical aspects of medicinal and non-medicinal substances,
 preoperational aspect, content, intensity and standards and
 criteria’s to be fulfilled related to such particulars ( EFMHACA).
21

22. 22
 To protect the user (patient, pharmacist,
manufacturer, government office, health
authority) against drugs of poor quality.
 To guarantee /ensure that the analytical
methods used are
 standard, keep breast of recent developments
Reasons for having a standard:

23. 23
1. Description
2. Minimum standard of purity
3. Identification tests
4. Limit tests to exclude excessive impurities
5. Physical constants
6. Storage conditions and packaging
7. Labeling
8. Dosage
9. Therapeutic category
10. Quantitative assays
Contents of Official monographs

24. 24
Contents of Official monographs…………..cont’ d
 Titles:
 Main titles
 Subsidiary titles or synonyms
 Molecular formula and
 molecular weights
 Chemical names have also been provided
 Identification:
 Tests for identity are provided only as an aid to identification.

25. 25
 Dosage:
• Doses mentioned in monographs are intended for general
guidance
 Minimum standards of purity and Assay Tolerance:
• Upper limit is not stated, the upper limit is not more than the
equivalent of 100.5%.
• The range is inclusive of the two limits and values outside the
range is not acceptable
• allow for
– analytical errors
– variations in manufacture and compounding

26. 26
Description:
• Is relatively general in nature
• It is provided to indicate the properties of the chemicals.
• The properties are not in themselves standards or
tests for purity though they may help in the
preliminary evaluation of chemical.
Solubility:
• are provided primarily as information.
• However, where quantitative solubility test is given
under standards the drug should comply with all
these requirements.
E.g. Very soluble
Freely soluble

27. 27
Packaging, storage and labeling:
 The container should
– not interact physically or chemically with the chemical
– be sight sensitive,
– well-closed, etc…
 Storage conditions;
 Cold: any TO not exceeding 8O and usually between 2O and 8O
C.
 Cool: Any TO between 8O and 25O
C.
 Room Temperature: TO prevailing in working area
 Warm: Any TO between 20O and 40O
C.
 Excessive heat: Any To above 40O
C.

28. 28
 Where no specific conditions are indicated it is to be
understood that storage conditions includes protection
from moisture, freezing and excessive heat.
 In general labeling of drugs and pharmaceuticals is
governed by Dugs and Cosmetic Act.
 Additional information which must be stated on label is
mentioned in the monograph.

29. 29
 Physical constants:
 are characteristic properties useful for both identification and
maintenance of standards of purity
 included in monograph for the standardization of pharmaceuticals.
These are:-
o melting point,
o boiling point,
o refractive index,
o optical rotation,
o light absorption,
o solubility etc..

30. 30
Quantitative Assays:
• Another test commonly performed in the QC
laboratory is the assay.
• This test is used to determine the purity of an
active substance or the amount of an active
ingredient present in a dosage form.
 Assay methods
specific for the chemical
stability determination

31. Quantitative analysis
31
 The procedures of quantitative analytical chemistry are applied to the
analysis of materials used in pharmaceuticals.
 In analytical chemistry , there are mainly two types of analytical methods
based upon the determination type. They are as follows:
– Qualitative analysis (what a substance is composed of
)
the presence or absence of one or more components and
– Quantitative analysis (exactly how much)
how much of the pure component is present
 There are various methods of quantitative analysis.

32. 32
Steps in atypical quantitative analysis
1. Formulating the questions to be answered through chemical
measurement
2. Selecting analytical procedures
– search the chemical literature
– developing original procedure
3. Sampling
– bulk sample

33. 33
4. Sample preparation
1. homogenous laboratory sample
2. converting lab. sample to the one suitable for analysis
– dissolving, making concentration prior to analysis
3. extraction–to remove mask species or interferences.
5. Analysis
– clear written report with limitations.
6. Reporting and interpretation
– conclusions should be consistent with the data.

34. Various methods of quantitative analysis
 Analytical method used to achieve Qualitative and
quantitative analysis include :
1. Chemical methods
a) volumetric methods:
– Assay is based on the measurement of volume of
solution of known strength that is required to react
completely with the substance to be analyzed.
– preferred to gravimetric processes especially because of speed
and convenience. 34

35. Chemical methods cont ...
 depending up on the type of reactions involved:They are:
- Neutralization titrations
- Precipitation titrations Ion combination rxn
- Complexometric titrations
- Oxidation reduction titrations electron transfer rxn
35

36. Various methods Cont’
b) Gravimetric methods:
 Gravimetric analysis is a quantitative analysis by weight
 it is a process of isolating and weighting the compound of
known composition
 The separation of compound is affected by number of ways
like precipitation, volatilization, etc
36

37. 37
C. Gasometric methods:
 involve measurement of the volume of gases.
 They measure the:
– volume of gas librated in the given chemical reaction
under the conditions that are described in the process

38. Various methods Cont’
2. Instrumental methods
 Based on the relation between the content and corresponding
physicochemical properties of the substance being analyzed.
 The changes in the properties of the system are generally
detected through the measurement of
 current,
 potential,
 electrical conductivity,
 optical density,
 refractive index etc. with suitable and sensitive instruments.
38

39. A/ Electrochemical method:
 It measures current, potential, electrical conductivity, etc. with
suitable and sensitive instruments.
E.g. Potential – potentiometery.
current – amperometry
Voltametry, conductometry etc
39

40. Various methods Cont’
B/ The chromatographic methods:
Chromatography is a separation technique or a device
by which a mixture of substances is separated into its
various components.
Used for identification & quantification of different
pharmaceuticals.
E.g. column, paper, thin layer, gas, ion exchange,
HPLC, etc.
40

41. Various methods Cont’
C/ Optical method
- measures the amount of light absorbed, scattered, emitted or
transmitted by the sample solution. - it include:
i) light absorption method
- UV/visible spectrophotometry
- IR spectrometry
- AA spectroscopy
41

42. Various methods Cont’
ii) light scattered method
- Nephlometry & turbidometry
iii) light emitted method
- Emission spectroscopy
- Fluorimetry
42

43. Various methods Cont’
3) Microbiological methods
Antibiotic sensitivity test.
 The microbiological assay is based up on a comparison of
the inhibition of growth of bacteria by measured
concentration of antibiotics to be examined with that of
a known concentration of standard preparation of the
antibiotic.
 The inhibition of microbial growth under the standard
conditions may be utilized for knowing therapeutic efficacy
of antibiotics.
 Very important for resolving doubts regarding possible loss
of potency of antibiotics and their preparations.
43

44. Microbial limit test
(bioburden test& specific desiginated test)
Sterility test
Pyrogen test
44

45. Selecting an analytical method
 In order to select an analytical method intelligently, it is
essential to define clearly the nature of the analytical
problem.
 In general, the following points should be considered when
choosing an instrument for any measurement.

46. 1. Accuracy and precision required
2. Available sample amount
3. Concentration range of the analyte
4. Interference in sample
5. Physical and chemical properties of the sample matrix
6. Number of sample to be analyzed
7. Speed, ease, skill and cost of analysis