HPLC测定双硫仑原料药中的有关物质并考察其稳定性

Determination of the related substances in Disulfiram by HPLC and investigation of the stability

目的采用RP-HPLC法测定双硫仑原料药中的有关物质,并进行稳定性考察。方法采用Shiseido Capcell PAK C18色谱柱(250 mm×4.6 mm,5μm),流动相为乙腈-水(50∶50),流速1.0 m L·min-1,检测波长210 nm,柱温25℃。结果双硫仑与有关物质能够得到良好的分离;双硫仑的检测限为0.05μg·m L-1;在各影响因素条件下,双硫仑的外观性状无明显变化,但含量均有所下降,有关物质有所增加;在加速试验和长期试验中,双硫仑的外观性状、含量及有关物质均无明显变化。结论双硫仑原料药中的有关物质符合限度要求,且在贮存过程中基本稳定,符合《化学药物稳定性研究技术指导原则》中对原料药稳定性的要求。

OBJECTIVE To determine the related substances in Dsulfiram by RP - HPLC and investigate the stability. METHODS Shiseido Capcell PAK Cls column （250 mm ×4.6 mm, 5 μm） was used with a mobile phase of acetonitrile- water （50 ： 50） and the flow rate was 1.0 mL· min^-1. The detection wavelength was 210 nm and column temperature was 25 ℃. RESULTS Related substances were completely separated from Disulfiram. The lowest examination limit of Disulfiram was 0.05 μg· mL^-1. Under all the stress testing conditions, the appearance of Disulfiram had no obvious change, and the content decreased and the related substances increased. During long - term storage and accelerated storage testing, the appearance, content and related substances of Disulfiram had no evident change. CONCLUSION The related substances in Disulfiram meet requirement. During stored procedure, Disulfiram is basically stable and consistent with what Guidance for stability of Chemical Drug requires.