雷贝拉唑钠肠溶片有关物质的检测方法研究

Determination of the Related Substances in Rabeprazole Sodium Enteric-coated Tablets

建立了HPLC法测定雷贝拉唑钠(1)肠溶片中的有关物质,即美国药典(USP 40)收录的杂质A~F。色谱柱采用Thermo Hypersil BDS C柱(4.6 mm×250 mm,5 μm),流动相A为乙腈∶4.35 g/L磷酸氢二钾溶液(用磷酸调至pH 7.0)(5∶95),B为甲醇,C为乙腈,梯度洗脱。检测波长为280 nm,柱温为45 ℃,进样量为5 μl。结果显示,1在0.3~102.5 μg/ml内线性关系良好,检测限为0.3 ng。1峰与各杂质峰能完全分离,且辅料不干扰测定。较《中华人民共和国药典》2020年版原有方法,本法可准确测定1肠溶片(共21批)中的共有杂质(杂质A),同时增加控制了已知杂质B、C和F,为1标准提高及药典标准的制定提供了参考。

An HPLC method was established for the determination of the related substances specified in US pharmacopoeia 40 as impurities A to F in rabeprazole sodium(1) enteric-coated tablets.The Thermo Hypersil BDS Ccolumn(4.6 mm×250 mm,5 μm) was used,and the analysis was carried out in the gradient elution mode with acetonitrile∶4.35 g/L dipotassium hydrogen phosphate solution(adjusted to pH 7.0 with phosphoric acid)(5∶95) as mobile phase A,methanol as mobile phase B,and acetonitrile as mobile phase C.The detection wavelength was 280 nm,the column temperature was 45 ℃,and the injection volume was 5 μl.The results showed that it was linear for 1 in the range of 0.3-102.5 μg/ml,and the detection limit was 0.3 ng.The peaks of 1 and each impurity could be completely separated,and the excipients did not interfere with the determination.Compared with the method in Chinese pharmacopoeia 2020,the established method not only could accurately determine the common impurity(impurity A) found in twenty-one batches of 1 enteric-coated tablets,but also control other three known impurities(impurity B,C,F),which provided a reference for the improvement of the specification on active pharmaceutical ingredient and the formulation of 1.