quality assurance vs quality control
quality assurance
- proactive
- process oriented, focus on preventing quality issues from arising
- control overall methods and procedures, ensure no contaminant in meds, ensure patient safety, protect against negative publicity, continually increase product efficiency, guarantee compliance
- roadmap for creating high quality products
- involve entire team
quality control
- reactive
- product oriented, focus on quality of manufactured products
- control parts of processes required to manufacture product
- verification of products in post manufacture stage
- involve dedicated technical personnel
key components of good manufacturing practice (GMP)
1) primary materials
- pure/starting materials used must be pure
2) premises
- premise/equipment maintained for operational readiness
3) competent people
4) latest technology and science for procedures
5) processes documented to show compliance
ICH
standardise validation of analytical processes
1) identification test
2) quantitative test for impurities
3) limits test for control of impurities
4) quantitative tests of the active pharmaceutical ingredients, drug products and selected components in drug products
sources of impurities
1) raw materials
2) method of manufacture
3) atmospheric contaminants
4) manufacturing hazards
5) inadequate storage
what are litmus tests used for
limit amount of impurities in drug
tldr methods for litmus tests
1) comparison method
2) quantitative determinants
litmus test - comparison method
- standard w define amt of impurity set up at same time and condition as test experiment
- extent of reaction determined by comparison of test solution and standard solution
- chlorides, sulphates, iron, heavy metals
litmus test - quantitative determinants
1) limits of insoluble matter
2) limits of soluble matter
3) limits of moisture, volatile matter and residual solvents
4) limits of non-volatile matter
5) limits of ignition
- limits of residue after ignition
- ash values
** measure amt of ash left after incineration
** high ash value = contamination, substitution, carelessness
for inorganic salts of carbonates, phosphates or silicates of Na, K, Ca, Mg
precipitation method
tldr types of identification tests
1) infrared absorption
2) ultraviolet absorption
3) thin layer chromatographic tests
infrared absorption
- compare IR spectrum of test and USP reference standard
- IR absorption relate to stretching and bending of bonds in different functional groups to structure of analyte
- used to identify functional group
ultraviolet absorption
- compare UV absorption/spectrum between test and standard solution using 1cm cell over 200-400nm
- determine absorptivity +/- absorption ratios in monograph
- meet requirements if same wavelength for maxima and minima and within specified limits
- conditions: solvent 5µg/mL, medium 0.1N hydrochloric acid in methanol (1:100)
thin layer chromatographic test
- more qualitative
- compare Rf values between 10µL of test solution w 10µL of USP reference standard
- requirements met if Rf value of principal spot similar
- conditions: 1mg/mL methanol, solvent system containing mixture of methylene chloride and methanol
- less precise than HPLC
application of titrimetric analysis
determine purity of API/raw materials
advantages and disadvantages of titrimetric analysis
advantages
1) high degree of precision and accuracy
2) robust
3) automated and cheap
disadvantages
1) not selective
2) Time consuming
3) large amount of sample and reagent
what are primary standards
- stable chemical compound in high purity
- used to standardise standard solution
- used to determine correction factor
formula for correction factor
f = (actual concentration/desired or normal concentration) x 100%
what correction factor values mean
1) f < 1
- actual concentration < desired concentration
- adjusted = measured conc x correction factor
2) f = 1
- actual concentration = desired concentration
3) f > 1
- actual concentration > desired concentration
- adjusted = measured / correction factor
recall how to calculate molarity
molarity = no. of moles of solute / vol of solution (L)
determining equivalence
1) determine reaction eqn
2) determine number of moles of thing we know using molarity equation if required
3) number of moles from ^ = number of moles of the thing we are finding
4) MW x number of moles of the thing we are finding = equivalent mass
tldr types of titration
1) indirect (back) titration
2) argentometric titration (Direct)
steps for indirect titration
add standard to weight amount of analyte then determine unreacted standard
indication for indirect titration
1) volatile substance (ammonia, volatile oil)
2) insoluble substances
3) substances for which quantitative reaction proceeds rapidly only in excess of reagent (lactic acid)
4) substance which require heating w volumetric reagent during determination in which loss of product can occur in process (aspirin)
blank titration for indirect titration
- required when heating liquid containing excess of standard alkali, cooling and back titrating excess
- ensure changes in strength of standard accounted for
calculation for indirect titration
amount of analyte = (titre of standard in blank - titre of standard in expirement) x (correction factor for standard) x (equivalence of analyte)
