The Medicine
BP and Pharmaceutical Analysis
Drug: Analysis and Quality Control
• Impurity sources:
o Raw materials
o Manufacturing method
o Decomposition
o Environment
• Important characteristics to check:
o Identity, Purity, Uniformity
o Potency, Efficacy, Toxicity
o Packaging, Labelling, Storing stability
Practical Skills- Theoretical Basis
• Extraction and ID drugs: UV, IR TLC, Spot-test extraction techniques
• Content uniformity/standardisation of reagents: Volumetric analysis
• Quality Assurance: Synthesis and quality control of acetylsalicylic acid parent
substance. BP assay of formulated aspirin tablets
• Stability and Biological Activity: Effect on potency of an enzyme inhibitor
European/British Pharmacopoeia Official Compendia
• Defines requirements for:
o Quantitative and qualitative composition of medicines
o Tests to be carried out on medicines and substances and materials used in their
production
• Products labelled BP, must conform to standards in current BP, or if labelled BP1963,
then it must conform to BP1963 standards
• Monographs contain essential tests that provide verification of the suitability of he
product for pharmaceutical use. Also tests for identification and quantification of
specific impurities
What is in a monograph?
• Description of the product
• Identification tests
• Physical constants
• Minimum purity standards on Assay of active
• Pharmaceutical ingredients
• Limit Test. Controls impurity levels
• Storage conditions
,The Medicine
Using BP information
• Solubility statements are just a guideline. When it’s stated elsewhere e.g. under
headings such as “Solubility in Ethanol” then it’s a requirement
o Soluble means 1g in < 30ml,
o Slightly soluble 1g in 100ml – 1L
o Practically insoluble (1g in >10L)
• ID Tests: Not absolute proof- only to verify that the identity is according to label claim.
IR reference spectra are for comparison ad main peaks should match
• Visual comparative tests conducted in identical tubes with flat base tubes. Nessler
cylinder
• Assays- Quantity taken for assay must not deviate by more than 10% from that stated
• Weighing- Accuracy to +/- 5 units after the last figure
• Volumes & apparatus: If the figure after the decimal point is a zero or ends in a zero
(for example, 10.0ml or 0.50ml), use a pipette, a volumetric flask, or a burette to
measure. Otherwise use a graduated cylinder/pipette. For volumes stated in
microlitres range use micropipette or a microsyringe
• Drying- Drying to constant mass implies +/- 0.5mg difference in weight between 2
dryings. Loss on drying reflects the net weight of a pharmaceutical substance under
certain specified conditions of heat, pressure, or duration
• Limit tests: Standards are used to control the presence of toxic impurities through
prescribed “limit tests”- Often by comparing colour or turbidity of a prescribed
solution against standard solution with known amounts of impurities
Nessler cylinders
• Run tests in these and observe solution from above to see which has stronger/weaker
colour intensity if any. One can be a reference and another test sample. Could have a
3rd system suitability test.
• Analysis tells us if the formulation (drugs, impurities, excipients) meets certain
specification quantitatively and qualitatively.
,The Medicine
Measurement and Data Reliability
Steps in drug analysis
Steps in analysing a sample
• Sample: Select a representative
• Extraction: E.g. is a lot of matrix present?
• Purification: E.g. is the test highly susceptible to impurities, excipients, and
degradation products?
• Characterisation: Target analyte should be identified, especially if the test is not very
specific
• Data Validity: Determine through stats, comparison with standards and/or another
method. If you are testing a newly developed method or if thee method has been
changed significantly then it is critical to validate new method first
Presenting and Handling Analytical Data
• Can you group it- Frequency table- histogram if numerical or bar chart if No. and text
• Did you change only one parameter- Line graph with x axis being independent variable
• >1 parameter- Scattergram
Linear Regression Analysis
• Better than manual determination
• y= a + bx
• a and b are parameters of the line. b= slope. a= y intercept
• N= No. of pairs of values
, The Medicine
Measurement and Uncertainty
• Some numbers are exact- No uncertainties
• Analytical measurements aren’t exacts- Assume that the last digit quotes in a
measured value is uncertain
• Assaying the drug content: Drug content stated is different for different drugs and may
have a wide range- 90-99.9% therefore when calculating % of the chain (stated
content) it is a good idea to round up to 3sf at the end of calculations
Validity of Analytical Measurement
1. Indeterminate (random) error: Evaluate with stats. Affects precision more than
accuracy. Follow the normal distributions
2. Determinate (systematic) error: Evaluate with standards
3. Gross error: Big mistake
• Precision- How close (respectable) are the measurements to each other
• Expressing precision:
o Range
o Standard deviation
o σ= Measure of precision
Do then all within the bracket and add them up. Then divide by the number there are. Then
square root it to find the answer
• X bar is for a set of numbers
• Mew (micrometre) for a population (lots of numbers)
Relative Standard Deviation (RSD)
Also called the coefficient of variation
Accuracy
• How close a measurement is to accepted value. Calculate absolute error to evaluate
accuracy
BP and Pharmaceutical Analysis
Drug: Analysis and Quality Control
• Impurity sources:
o Raw materials
o Manufacturing method
o Decomposition
o Environment
• Important characteristics to check:
o Identity, Purity, Uniformity
o Potency, Efficacy, Toxicity
o Packaging, Labelling, Storing stability
Practical Skills- Theoretical Basis
• Extraction and ID drugs: UV, IR TLC, Spot-test extraction techniques
• Content uniformity/standardisation of reagents: Volumetric analysis
• Quality Assurance: Synthesis and quality control of acetylsalicylic acid parent
substance. BP assay of formulated aspirin tablets
• Stability and Biological Activity: Effect on potency of an enzyme inhibitor
European/British Pharmacopoeia Official Compendia
• Defines requirements for:
o Quantitative and qualitative composition of medicines
o Tests to be carried out on medicines and substances and materials used in their
production
• Products labelled BP, must conform to standards in current BP, or if labelled BP1963,
then it must conform to BP1963 standards
• Monographs contain essential tests that provide verification of the suitability of he
product for pharmaceutical use. Also tests for identification and quantification of
specific impurities
What is in a monograph?
• Description of the product
• Identification tests
• Physical constants
• Minimum purity standards on Assay of active
• Pharmaceutical ingredients
• Limit Test. Controls impurity levels
• Storage conditions
,The Medicine
Using BP information
• Solubility statements are just a guideline. When it’s stated elsewhere e.g. under
headings such as “Solubility in Ethanol” then it’s a requirement
o Soluble means 1g in < 30ml,
o Slightly soluble 1g in 100ml – 1L
o Practically insoluble (1g in >10L)
• ID Tests: Not absolute proof- only to verify that the identity is according to label claim.
IR reference spectra are for comparison ad main peaks should match
• Visual comparative tests conducted in identical tubes with flat base tubes. Nessler
cylinder
• Assays- Quantity taken for assay must not deviate by more than 10% from that stated
• Weighing- Accuracy to +/- 5 units after the last figure
• Volumes & apparatus: If the figure after the decimal point is a zero or ends in a zero
(for example, 10.0ml or 0.50ml), use a pipette, a volumetric flask, or a burette to
measure. Otherwise use a graduated cylinder/pipette. For volumes stated in
microlitres range use micropipette or a microsyringe
• Drying- Drying to constant mass implies +/- 0.5mg difference in weight between 2
dryings. Loss on drying reflects the net weight of a pharmaceutical substance under
certain specified conditions of heat, pressure, or duration
• Limit tests: Standards are used to control the presence of toxic impurities through
prescribed “limit tests”- Often by comparing colour or turbidity of a prescribed
solution against standard solution with known amounts of impurities
Nessler cylinders
• Run tests in these and observe solution from above to see which has stronger/weaker
colour intensity if any. One can be a reference and another test sample. Could have a
3rd system suitability test.
• Analysis tells us if the formulation (drugs, impurities, excipients) meets certain
specification quantitatively and qualitatively.
,The Medicine
Measurement and Data Reliability
Steps in drug analysis
Steps in analysing a sample
• Sample: Select a representative
• Extraction: E.g. is a lot of matrix present?
• Purification: E.g. is the test highly susceptible to impurities, excipients, and
degradation products?
• Characterisation: Target analyte should be identified, especially if the test is not very
specific
• Data Validity: Determine through stats, comparison with standards and/or another
method. If you are testing a newly developed method or if thee method has been
changed significantly then it is critical to validate new method first
Presenting and Handling Analytical Data
• Can you group it- Frequency table- histogram if numerical or bar chart if No. and text
• Did you change only one parameter- Line graph with x axis being independent variable
• >1 parameter- Scattergram
Linear Regression Analysis
• Better than manual determination
• y= a + bx
• a and b are parameters of the line. b= slope. a= y intercept
• N= No. of pairs of values
, The Medicine
Measurement and Uncertainty
• Some numbers are exact- No uncertainties
• Analytical measurements aren’t exacts- Assume that the last digit quotes in a
measured value is uncertain
• Assaying the drug content: Drug content stated is different for different drugs and may
have a wide range- 90-99.9% therefore when calculating % of the chain (stated
content) it is a good idea to round up to 3sf at the end of calculations
Validity of Analytical Measurement
1. Indeterminate (random) error: Evaluate with stats. Affects precision more than
accuracy. Follow the normal distributions
2. Determinate (systematic) error: Evaluate with standards
3. Gross error: Big mistake
• Precision- How close (respectable) are the measurements to each other
• Expressing precision:
o Range
o Standard deviation
o σ= Measure of precision
Do then all within the bracket and add them up. Then divide by the number there are. Then
square root it to find the answer
• X bar is for a set of numbers
• Mew (micrometre) for a population (lots of numbers)
Relative Standard Deviation (RSD)
Also called the coefficient of variation
Accuracy
• How close a measurement is to accepted value. Calculate absolute error to evaluate
accuracy
