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Essays:
1. What is the purpose of Q.C of drug products? Enumerate/ Explain
2. Enumerate 5 rules for caring weighing balance.
3. Describe the term constant weight
4. How is proper “washing” of precipitates done?
5. How is drying and ignition of Sx and ppt. carried out?
Quality- sum of all factors which contribute directly or indirectly to the safety, effectiveness and reliability of a product.
A course in quantitative pharmaceutical chemistry should be designed to meet the following objectives:
1. Knowledge of basic principles.
2. Awareness of drug quality and quality control.
3. Basic principles of clinical laboratory methods.
4. Basic chemical concepts.
Quantitative Pharmaceutical Chemistry- may be defined as the application of the procedures of quantitative analytical
chemistry:
When the quality of a drug product is challenged by a physician, the pharmacist is responsible for initiating steps to
determine if the product is defective. This may be accomplished by:
1. Calling and advising the drug manufacturer of the problem involving the product.
2. Analyzing the preparation in the prescription laboratory barrowing needed equipment from a clinical laboratory if
necessary.
3. Sending a portion of the sample to a private laboratory for analysis.
4. Combination of all these steps.
*Improper labeling, discoloration, the presence of cloudiness, crystals, or precipitates in products known to be solutions.
Quality- sum of all factors which contribute directly or indirectly to the safety, effectiveness and reliability of a product.
United States Pharmacopeial Convention, Inc., a nonprofit corporation composed of representatives from all accredited
colleges and schools of pharmacy and medicine in U.S.
Methods of analysis in quantitative pharmaceutical chemistry may be appropriately subdivided according to the following
procedures, each of which requires a special technique.
Volumetric analysis is the determination of the volume of a solution of known concentration required to react with a given
amount of a substance to be analyzed.
Physicochemical methods of analysis are based on some specific physical or chemical property or properties of the
substance being analyzed. In many assays the measurement of these properties requires the utilization of an instrumental
technique (e.g. Chromatographic, Spectrophotometric, Electrometric, Thermal Conductimetric, Refractometric, and
Polarimetric ).
Gravimetric analysis is the separation by extraction, precipitation, or other means of the constituent to be determined
either in the natural state or in the form of a definite compound the composition of which is known to the analyst, and the
weighing of the resulting product.
Special methods are those which require a distinct type of technique, such as alkaloidal assaying.
Official assay method serve as an exact measure of the purity of a substance only when the results are considered in
conjunction with the qualitative tests.
Chapter 1
REMARKS AND GENERAL DIRECTIONS
Success as an analyst
Important objective in studying qpc is the acquisition of a fundamental knowledge of the theory as well as a practical ability
in the application of analytical methods. The analyst must require skill of technique, patience, neatness and accuracy.
Notebooks
The date is very important in all scientific work. Numerous legal decision have been lost through the failure of the analyst to
affix the date at the time of analysis.
Economy of time
Clean desk, clean apparatus, label all solutions, keep two operations going at one time, utilize all times between operations.
Cleaning Solution
200 g sodium dichromate in 100 ml water, adding 1500 ml sulfuric acid (XIX (U.S.P.,p.675))
Wash Bottles
Used in quantitative work. Consist of rubber-stoppered, flat-bottomed flasks of 500- to 100-ml capacity fitted with
smoothly bent tubes and a jet made flexible by means of a rubber joint. Wash bottles made of polyethylene are also suitable
for quantitative analysis.
Policeman
Is a piece of soft rubber tubing fitted to the end of a glass rod. It is used to loosen from the walls containing vessel
adhering particles that are not removable by a stream of water from the wash bottle. A policeman should never be used as a
stirring rod or allowed to remain analytical solutions.
Reagents
Must be pure. “Analyzed” or “Reagent” grade meet the specifications of American Chemical Society.
Materials Required
All reagent materials should meet the official requirements of purity and strength.
SAMPLING
The first important consideration in an analysis is the securing of a representative sample, a consideration too frequently
ignored by analysts. Fixed rules cannot be laid down in sampling, for much depends on the nature of the material and the
quantity from which the representative sample is to be taken. Whenever possible, a sample from each package should be
examined separately. When a single package s sampled, the contents should be mixed or samples should be taken from
different parts of the container and mixed, and then a portion of this mixture should be taken for analysis.
Accuracy is used to denote the agreement of an experimental result or the agreement of the mean value X of a series of
experimental results with the true value, and is usually expressed in terms of error.
Absolute error the difference between the mean and the true value.
Relative error is found by dividing the absolute error by the true value. Usually reported on a percentage basis. PPH or PPT
Average deviation d is calculated by finding the differences between the individual results and the mean, regardless the
sign, adding these differences and dividing by the number of determinations.
Relative Average Deviation is found by dividing the average deviation by the mean. Expressed in PPT.
Standard Deviation s is calculates using the equation found in S…….. and is the preferred measure of precision.
Relative Standard Deviation, sometimes called the coefficient of variation, is found by dividing the standard deviation by
the mean and multiplying by 100.
Range is the difference between the largest and smallest results in a series of measurements.
Significant Figures
Significant figures in a number are defined as all certain digits of a measurement plus one doubtful digit.
General operations
Crucibles
A variety of crucibles is used in quantitative analysis. Those most common employed are made of high-grade porcelain. They
withstand high temperature and are suitable for use in the ignition of most drugs and precipitates. Not suitable for fusions.
Fused silica, alundum, nickel, and platinum.
The gooch filtration crucible is designed for the separation of precipitates by suction filtration. Bedded with Asbestos, thus
making it possible to collect, wash, dry, and weigh a precipitate in the same crucible.
Fritted-Glass Crucibles
Fritted-glass crucibles have fused-in sintered or fritted-glass bottoms and are supplied in various porosities such as medium
and fine.
Evaporation of Liquids
The evaporation of liquids is best carried out in porcelain dishes constructed for that purpose, which expose a large surface
of liquid to the air.
Transfer of Liquids
As few transfers of liquid as possible should be made, since each is possible source of error. When transfers are necessary,
they must be made quantitatively, washing the original container with successive small portions of wash liquid.
Constant Weight
Dried to constant weight means that two consecutive weighings do not differ by more than 0.5 mg/g of substance taken for
determination, the second weighing following an additional hour of drying.
Use of Dessicators
Dessicators are a special form of glass vessel, rendered airtight by means of ground contact surfaces, used to maintain a
dry atmosphere for objects that might be affected by moisture or carbon dioxide.
Weighing Procedures
1. Before Weighing
2. Zero the balance
3. Preweigh
4. Weigh
5. Final Step
Weights
Should meet standards.
Quality Control (Week 1)
Volumetric Analysis
Titration, Titrant and Analyte
Analytical Chemistry- branch of chemistry which provides information relative to its composition of matter. AKA
Pharmaceutical Chemistry.
Pharmaceutical Chemistry
1. Qualitative Method of Analysis- the process of determining the elements or compounds present in the give sample.
2. Quantitative Analysis- the process of determining the proportions in which the various elements or compounds are
present.
Quality- is the combination of attributes or characteristics of a product which, when compared to a standard, serves as a
basis for measuring the uniformity of the product and determines its degree of acceptability.
Official Compendia- approved sources of guidelines for drug quality required by certain practitioners or agency.
USP, NF, British Formulary
The complete MONOGRAPH of a raw material or finished dosage form includes the following information:
a. chemical structure
b. chemical name
c. Purity rubric
d. Packaging and Storage
e. Reference Standard
f. Identification Test
g. Corresponding tests for chemical and physical constants such as melting-range, rotary power, refractive index.
h. water content
i. Assay procedure
Control- refers to the measure or step that is used to prevent or eliminate drug risks/hazards to make it safe and
effective.
Quality Control- is a tool, which gives the assurance that a product conforms to standards and specifications through the
system of inspection, analysis and action. Assures that a drug product is safe, pure and effective. Is product oriented and
focuses on defect, identification.
Quality Assurance- the sum total of the organized activities performed. Focuses on defect prevention.
C. Special Methods
Analysis which require a distinct type of technique such as analysis of crude drugs, assay of fats and fixed oil,
assay of volatile oils and assay of alkaloids.
D. Physico-chemical Methods
Analysis based on some specific physical and chemical property or properties of the substance being analyzed with
the use of instrument such as:
- Spectrophotometer
- Chromatograph Unit
- Polarographer
- Polarimeter
- Fluorometer- Fluoride Content
Control Functions
- May appear varied and never quite identical in any way.
1. MONITOR FUNCTION- is to assure that even though production personnel have primary responsibility for control over
their processes, these processes are maintained and that any deviation for specified requirements is reported. Conducts
environmental monitoring. This is to control the microbial and particulate matter content of environmental air in areas where
pharmaceuticals such as parenterals are processed.
2. ANALYSIS FUNCTION- Conducts testing not only on the raw materials and packaging components but also on the bulk
product during processing and after packaging prior to its release to the market and continues even after distribution to the
end user when selected lots are subjected to shelf life studies to confirm the expiration period of the finished product.
3.RECORD, REVIEW AND RELEASE FUNCTION- to determine accuracy and completeness of all records generated during
the cause of production prior to the release of each lot finished product to the market.
A detailed checklist is frequently employed by the employer.
4. AUDIT FUNCTION- to train employees to comply with the SOP’s and to understand why and how these SOP’s are to be
followed. Quality audit is designed to detect areas where the established SOP’s are not being followed and to these findings
to the supervisor for appropriate action.
QC and Pharmacist
Pharmacist must have working knowledge if they are to advise medical practitioners on drug quality. Is responsible for
initiating steps to determine if a product is defective. He is also responsible for solving problems related to drug quality.
Methods of Analysis
Sampling- process of removing an appropriate number of items from a population in order to make influences to the entire
population.
Population- is the totaling of all actual or conceivable items of a certain class under consideration.
Sample- is a finite number of subjects selected from a population.
Random sample- is a sample chosen in such a manner that one object has a good chance of being selected as another.
Assay- process of determining the potency, strength, or percentage purity of a drug or preparation.
Classification of Analysis
Absolute error- Difference between the mean value and the true value
E. Absolute= Mean Value- True Value
Relative Error- Absolute error divided by true value.
E. Relative= E. Absolute/ True Value
Outline:
- Volumetric Analysis
-Neutralization reaction
- Indicators that can be used in neutralization reaction
- Types of Titration
- Modern Theories for Acid and Base
Volumetric Analysis
- Also known as TITRIMETRIC METHOD
- A solution of known concentration is added to solution of analyte until the reaction is judged complete.
- The experimental way of determining when equivalent amounts have reacted.