Stability indicating methods for the determination of clozapine

Abstract

Five new selective, precise and accurate methods are described for the determination of clozapine in the presence of its main degradation product. Method A utilizes the second and third derivative spectrophotometry at 315 and 305 nm, respectively. Method B is RSD 1 spectrophotometric method based on the simultaneous use of the first derivative of ratio spectra and measurement at 295 nm. Method C is a pH-induced difference (ΔA) spectrophotometry using UV measurement at 325 nm. Method D is a densitometric one, after separation on silica gel plate using methanol: water as mobile phase, and the spot was scanned at 295 nm. Method E is RP-HPLC using acetonitrile: water (40:60 v/v) as mobile phase at a flow rate of 1 ml/min and UV detection was at 295 nm. Regression analysis showed good correlation in the concentration ranges 3–10, 4–10, 10–25 μg/ml, 200–1000 ng/spot, 5–100 μg/ml with percentage recoveries of 99.4±0.28, 99.8±0.20, 100.05±0.11, 99.41±0.34, 100.11±0.07 and 100.07±0.05% for methods A, B, C, D and E, respectively. These methods are suitable as stability indicating methods for the determination of clozapine in the presence of its main degradation product either in bulk powder or in pharmaceutical formulations.