Measuring degradation

Question 1

In terms of drug stability, what does kinetics determine?

Answer 1

Extent of degradation over time

Question 2

What does long term stability testing involve?

Answer 2

storing the products under realistic worst-case conditions of temperature and humidity

Question 3

What are some limitations of accelerated stability?

Answer 3

1. kinetics of degradation may change at higher temperatures
2. Additional complex reactions may take place at higher temperatures
3. Temperature may change the nature of the dosage form
4. Change in physical properties with unpredictable effect

Question 4

What does accelerated stability testing help you calculate

Answer 4

using an Arrhenius plot you can find the value of K at any temperature and estimate shelf-life

Question 5

What problem does photodegradation cause in practice?

Answer 5

will reduce patient compliance

Question 6

What are some typical forced conditions?

Answer 6

Acid hydrolysis in 0.1M HCL
Base hydrolysis in 0.1M NaOH
Temperature 50-60 degrees Celsius 
Humidity 70-80%
Oxidation 3-30% peroxide 
Light irradiation

Question 7

What is the ideal range of degradation produced?

Answer 7

10-20%

Question 8

What is SIM testing and what does it do

Answer 8

Stability indicating method

Determines loss in API content and build up of degradation products

Question 9

What should a good SIM ideally be able to detect?

Answer 9

both API + degradation products simultaneously but not always possible.

Question 10

What do you measure for quantitative analysis

Answer 10

peak heights and peak areas (preferred)

Question 11

What is the external standard method?

Answer 11

concentrations calculated from the ratio of sample peak areas to the corresponding standard peak areas

Question 12

In a HPLC chromatogram, what does a stepper gradient mean?

Answer 12

more rapid change in solvent composition - so will elute analytes faster

Question 13

What is the internal standard method?

Answer 13

a more precise method, less chance of error from reproducibility & sample preparation concerns. Often used in pharmacokinetics where trace levels of drugs or metabolites are present in a biological matrix

Question 14

Explain how you would conduct a quantitative analysis using an external standard

Answer 14

1. Prepare standard solutions of known concentrations and run HPLC on each
2. Plot area vs conc to get calibration curve
3. Sample drug and dilute to conc that is around 50% on calibration curve
4. Run HPLC of sample and find conc from area or from equation of best fit

Question 15

Explain how you would conduct a quantitative analysis using an internal standard

Answer 15

1. Add standard to analysis mixture
2. Relative areas are compared and used to calculate conc
3. Preferably sample preparation should be same for both sample and standard. Although in some assays the standard can be added after extraction
4. Response factors are used to calculate unknown concentration by comparing sample solution with a calibration solution
   - The internal calibrant concentration is kept the same in both solutions

Question 16

Why are placebo standards important?

Answer 16

To distinguish background peaks