Pharmaceutical Analysis 1 Lecture

Quality Control Analytical Chemistry

- Evaluates, maintains and reference ● Qualitative - “What is in the sample?”
standard for substances. ● Quantitative - “How much is present in
- Ensures correct labelling of containers the sample?”
of materials and products. Quality control guarantees which reasonable
- Ensures stability of active limits:
pharmaceutical ingredients and product - Free from impurities
is monitored. - Contains the amount of the active
- Helps investigate complaints relating to ingredients stated on the label.
product quality - Physical, chemically and
- Participates in environment monitoring. microbiologically stable.
Quality - Provides optimal release of active
- Attributes / characteristics ingredients when the product is
- Compared to standard administered
- Basis for measuring the conformity Quality control for quality drugs:
- Determines the degree of acceptability. SHEWHART CYCLE - PDCA Approach (Plan,
Measurable criteria: Do, Check, Act)
1. Conformance - prescribed limits
2. Fitness for use - functionality of the Types of Analysis:
products 1. Based on sample size:
3. Reliability - function in the specified - Ultra Micro < 1mg
environment for a prescribed length of - Mirco: 1 - 10mg
time. - Semi micro: 10 - 100mg
4. Yield - high degree of acceptable units - Macro: 100 - 1000mg
produced 2. Based on extent of determination
5. Customer satisfaction - requires the a. Proximate - total amount of a
product to be safe, pure and effective. class/ group of active
Drug quality as our main business constituent.
-The grim reality: b. Ultimate - amount of a single
1. Poor quality medicines do not meet chemical species in a sample.
official standards for: Strength, Quality, 3. Based on the nature of methods:
Labeling, Purity, & Packaging a. Classical - Titrimetry,
2. Poor quality drugs result in serious Gravimetry.
health implications including b. Instrumental - Spectrometry,
- Treatment failure Polarimetry
- Increased morbidity c. Miscellaneous - water content,
- Development of drug resistance ash content, acid value (crude
- Adverse effects drugs)
- Mortality Standards and Monographs:
- Wasted resources ● USP / Phil Pharmacopoeia / NF
Drug quality in the world: - A book of public pharmacopeial
➔ Availability of substandard and standards
counterfeit drugs in disturbing proportion - Contains standards for
in many low-income countries. medicines, dosage forms, drug
➔ Lack of reliable drug quality assurance substances, excipients,
systems in many developing countries. medicinal devices, and dietary
Qualitative and Quantitative Pharmaceutical supplements.
Chemistry General Principles in Quality Control:
 Pharmaceutical Analysis 1 Lecture
● Accuracy (validity) - closeness to the to standards and specifications through a
true value system of inspection, analysis and action.
● Precision (reliability) - closeness to each Analytical Chemistry - branch of chemistry that
other- reproducibility / repeatability. involves separating, identifying and determining
Assignable causes for errors: the relative amounts of the components in a
- Materials sample of matter.
- Methods - Qualitative Analysis - reveals the
- Men chemical identity of the species in the
- Machine sample.
Standards: - Quantitative Analysis - establishes the
a. Pharmacopeial Standards relative amount of one or more species
-found in published monographs in the sample.
- USP/NF, BP,EP,PP
- Identity, physical tests, purity tests, 6 broad areas of applications:
assay, limit tests 1. Establish economic value
b. Regulatory Standard 2. Determining health hazards
- Mandated by regulatory 3. Diagnosis of disease
agencies 4. Controlling quality
- Phil PDEA, WHO, US PDEA 5. Relating properties to
- For regulation purposes. composition/structure
c. In-house Standard 6. Conducting research
- Unofficial General methods of analysis (used in official
- Generated by the manufacturer pharmaceutical analysis):
- Allow flexibility A. Volumetric/Titrimetric
- Mandatory in compliance to - Neutralization methods (in aqueous and
GMP. nonaqueous solvents)
Standards must cover the following points - Precipitimetry or Precipitation or
1. Formula Saturation methods
- Ingredients, Amount - Complex Formation (Complexation)
2. Raw material specification methods
- Characteristics, Permissible - Oxidation-Reduction (REDOX)
range of purity, From the methods
monograph 1. Neutralization
3. Standard Operating Procedure a. Alkalimetry - titration of acid with
4. Finished Product Specification standard alkali solution.
- Proper performance, Purity, b. Acidimetry - titration of base with
Safety, Stability standard acid solution.
5. Packing Material Standard 2. Precipitation
- Run on a high-speed line - A substance is titrated by
- Involves a complicated assembly precipitating it with a standard
- Functional solution of a precipitating agent.
- Compatible with the product - Based on reactions that yields
- Protect the product and assure ionic compounds of limited
stability solubility.
6. Test Methods 3. Complex Formation Methods
- Standardized and Validated - A substance is titrated by with a
Quality Control - is a tool that gives the standard reagent to the
assurance that a product/substance conforms 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.