A New Method for the Quantification of Ethyl Sulfate and Isopropyl Sulfate Contents in Abacavir Sulfate by Ion Chromatography.

Abstract

A predictable new method was developed and validated for the determination of ethyl sulfate (EtS) and isopropyl sulfate (IprS) contents in abacavir sulfate (ABS) drug substance by ion chromatography (IC). Ethyl alcohol, isopropyl alcohol and sulfuric acids were used in the manufacturing process of ABS. Therefore, there is a possibility to form respective sulfate impurities, i.e., EtSs and IprSs. Hence, a control strategy is required for EtS and IprS contents in ABS. Chromatographic separation of EtS and IprS contents in Abacavir sulfate was achieved on Metrosep A Supp 10 (250 mm × 4.0 mm) column and particles of 4.6 μm size. The mobile phase consists of buffer (3.2 mM Sodium carbonate and 1.0 mM of sodium bicarbonate) and acetonitrile in the ratio of 90:10 (v/v) with the flow rate of 0.6 mL min-1 by applying 30°C column oven temperature. The analytes were monitored by conductometric detector. The performance of the method was assessed by evaluating the specificity, linearity, sensitivity, precision, robustness and accuracy experiments. The limit of detection and limit of quantification values for EtS were 0.3 and 0.8 μg mL-1 and for IprS were 0.3 and 0.8 μg mL-1, respectively. The correlation co-efficient value of linearity experiment was 0.9999 for EtS, 0.9998 for IprS. The average recovery for EtS was 98.7% and for IprS was 100.9%. The method is robust for EtS and IprS contents and also specific from other common anions, i.e., chloride, bromide, nitrate, sulfate, methyl sulfate and methanesulfonic acids. The results proved that the validated method was simple and cost-effective for controlling EtS and IprS contents in ABS drug substance, and the method can be successfully applied in the quality control analysis.