Drug substances recovery, accuracy testing

Accuracy. In the quantitative method that is used to measure the heavy metal quantity in the drug substance, the accuracy is usually represented by the recovery rate obtained from a spiked recovery test where lead is added to the samples. Since the heavy metals limit test specified in monograph specifications is a test where the intensity of coloring of the samples with sodium sulfide is compared with that of the control solution, it is necessary to confirm that heavy metal components can be detected fully in the process of test solution preparation. The Heavy Metals Limit Test in JP specifies four preparation methods for the test solutions. An appropriate method will be selected and used for further testing. The test method that gives the best recovery rate is to be adopted. The procedure is as follows ... 

It is absolutely essential that the accuracy be validated with the same quantitation method that is used in the control test procedure. Recovery deviations from the theoretical values while performing a calibration with a drug substance alone may indicate interferences between the analyte and placebo components. In such a case, the calibration should be done with a synthetic mixture of placebo and drug substance standard. Such interferences may also be detected by the separate determination of linearity for dilutions of the drug substance and for a spiked placebo. 

Table 3 Investigation of accuracy by recovery. Drug substance was added in the solid state to a granulation of placebo tablets in a range from 80% to 120% of the nominal content of 50 mg. The further sample preparation is performed according to the control test...

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