STABILITY STUDY OF CAPECITABINE ACTIVE PHARMACEUTICAL INGREDIENT IN BULK DRUG AND PHARMACEUTICAL FORMULATION

Abstract

A simple, precise, and accurate gradient reverse phase-LC method was developed for quantitative determination of capecitabine (CPT) drug sample and drug products in bulk samples and pharmaceutical dosage forms. Accelerated tests for stability evaluation were performed at 40°C ± 2°C and 75 ± 5% relative humidity (RH), according to the current official guidelines. The samples were kept in a climatic chamber for 6 mo in the aforementioned conditions. The samples were withdrawn from the climatic chamber and analyzed periodically (0, 3, and 6 mo) by HPLC on an Eclipse XDB-C18 column (250 × 4.6 mm i.d. particle size is 5 µm), using a mobile phase of 0.02 M ammonium formate containing formic acid to maintain pH at 4.0-acetonitrile with gradient, at a flow rate of 1.0 mL min−1. The UV detector was operated at 240 nm while column temperature was maintained at 40°C. The unknown impurity at relative retention time (RRT) of 0.26 min ranged from 0.02 to 1.90% on an area-percentage basis and has been observed in reverse phase-LC of CPT drug substance and drug product in accelerated test at two time points, initial (0 mo) and 6 mo. Chemically, the impurity was identified as 4-amino-1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-pyrimidin-2(1H)-one. Utility of the developed method was examined by analyzing the tablets containing CPT. The results of analysis were supported by statistical parameters.