DEVELOPMENT OF STABILITY INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF RELATED SUBSTANCES IN ATORVASTATIN SOLID DOSAGE FORM AND BULK DRUGS

摘要

Objective: The present paper reports the development of simple, rapid, accurate and stability indicating reversed phase high-performance liquid chromatography method (RP-HPLC) for estimation of related substances in Atorvastatin calcium (ATV) bulk drug as well as in solid dosage form. The method was validated using Agela, Unisol C18 (250 mmX 4.6 mm; 5μ) column. Methods: A method was developed to separate clearly the drug peak from the synthetic/process impurities and degradation products formed under stress conditions is attained on (T/%B) were set at 0/43, 18/43, 20/60, 33/60, 35/43, and 40/43 of 0.02 mM ammonium acetate buffer of pH4.9 was used as mobile phase A and 90:10 v/v, ratio of acetonitrile and tetrahydrofuran was used as mobile phase B. A flow rate of 1.4 ml/min and column temperature of 25 °C was used. The wavelength selected was 246 nm. The developed method was validated as per ICH guidelines for the specificity, precision, linearity, accuracy, limit of detection, limit of quantitation and robustness. Results: Linearity of the impurities was accomplished in the range 0.3-6.0μg/ml for impurity A (Imp A), B (Imp B), C (Imp C), H (Imp H) and 0.4-6.0μg/ml for impurity D (Imp-D), correlation coefficient was found to be more than 0.999 for all impurities. Recovery of impurities was found to be in the range 93%-111%. Conclusion : The developed method was simple, precise, accurate, robust and also cost effective as it has shorter run time for quantification of impurities in drug substance and drug product as well. Keywords: Atorvastatin calcium, Impurities, ICH guidelines, Method development, Analytical method validation, Degradation.