QAQC

Question 1

quality assurance vs quality control

Answer 1

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

Question 2

key components of good manufacturing practice (GMP)

Answer 2

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

Question 3

ICH

Answer 3

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

Question 4

sources of impurities

Answer 4

1) raw materials
2) method of manufacture
3) atmospheric contaminants
4) manufacturing hazards
5) inadequate storage

Question 5

what are litmus tests used for

Answer 5

limit amount of impurities in drug

Question 6

tldr methods for litmus tests

Answer 6

1) comparison method
2) quantitative determinants

Question 7

litmus test - comparison method

Answer 7

• 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

Question 8

litmus test - quantitative determinants

Answer 8

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

Question 9

tldr types of identification tests

Answer 9

1) infrared absorption
2) ultraviolet absorption
3) thin layer chromatographic tests

Question 10

infrared absorption

Answer 10

• 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

Question 11

ultraviolet absorption

Answer 11

• 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)

Question 12

thin layer chromatographic test

Answer 12

• 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

Question 13

application of titrimetric analysis

Answer 13

determine purity of API/raw materials

Question 14

advantages and disadvantages of titrimetric analysis

Answer 14

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

Question 15

what are primary standards

Answer 15

• stable chemical compound in high purity
• used to standardise standard solution
• used to determine correction factor

Question 16

formula for correction factor

Answer 16

f = (actual concentration/desired or normal concentration) x 100%

Question 17

what correction factor values mean

Answer 17

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

Question 18

recall how to calculate molarity

Answer 18

molarity = no. of moles of solute / vol of solution (L)

Question 19

determining equivalence

Answer 19

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

Question 20

tldr types of titration

Answer 20

1) indirect (back) titration
2) argentometric titration (Direct)

Question 21

steps for indirect titration

Answer 21

add standard to weight amount of analyte then determine unreacted standard

Question 22

indication for indirect titration

Answer 22

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)

Question 23

blank titration for indirect titration

Answer 23

• required when heating liquid containing excess of standard alkali, cooling and back titrating excess
• ensure changes in strength of standard accounted for

Question 24

calculation for indirect titration

Answer 24

amount of analyte = (titre of standard in blank - titre of standard in expirement) x (correction factor for standard) x (equivalence of analyte)

Question 25

what is argentometric titration

Answer 25

involve measuring amount of precipitation between analyte and standard

Question 26

HPLC applications tldr

Answer 26

1) analyses based on calibration with external standard
2) analyses based on single point calibration
3) analyses based on calibration with internal standard

Question 27

HPLC analysis based on calibration w external standard

Answer 27

• fixed amount of analyte as standard, does not contain too many other components
• determine API or dosage form
• calculations
  ** actually j draw a concentration x peak area graph and a straight line through and plot out the data given and use ratio to guess

Question 28

HPLC analysis based on single point calibration

Answer 28

compare peak of analyte to calibration curve of standard

Question 29

HPLC analysis w internal standard requirements

Answer 29

1) X use standard analyte but similar structure
2) stable
3) can be chromatographically resolved from analyte -> same area, but peak well separated from analyte (Different peak height)
4) should elute as close as possible to analyte (peak X overlap)

Question 30

HPLC analysis w internal standard indication

Answer 30

biological fluid analysis, complex systems

Question 31

HPLC analysis w internal standard process

Answer 31

1) determine concentration ratio and peak area ratio for standard

• concentration ratio for = concentration of standard sample / concentration of internal standard
• peak area ratio = concentration of standard sample / concentration of internal standard

2) Calculate the concentration ratio and peak area ratio for the test solution with the same methods
3) use ratio of peak area ratio and concentration ratio of standard to determine concentration of test solution
4) value from ^ x concentration of internal standard to get concentration of test solution