柱前衍生化GC测定佐芬普利钙中间体光学杂质

Determination of Optical Isomer Impurity in the Intermediate of Zofenopril Calcium by GC with Pre-column Derivatization

关键词:  佐芬普利钙  中间体  光学杂质  气相色谱法  柱前衍生化

Key words:  zofenopril calcium  intermediate  optical impurity  GC  pre-column derivatization

摘要:

目的 建立测定佐芬普利钙中间体(S)-(-)-3-苯甲酰巯基-2-甲基丙酸的光学异构体杂质(R)-(+)-3-苯甲酰巯基-2-甲基丙酸含量的柱前衍生化GC。方法 以高纯试剂D-(+)-2-辛醇对(S)-(-)-3-苯甲酰巯基-2-甲基丙酸样品进行衍生化处理，衍生产物以Agilent DB-1701(30 m×0.53 mm，1.0 μm)柱为分析柱，以氮气为载气，流速为2.0 mL·min^-1，检测器温度为250 ℃，进样口温度为200 ℃，柱温为程序升温，进样量为1.0 μL。结果 光学杂质(R)-(+)-3-苯甲酰巯基-2-甲基丙酸在3.22~121.44 μg·mL^-1内线性关系良好(r=0.995 2)，定量限为3.22 μg·mL^-1，加样回收率为99.6%~102.4%，日内和日间精密度RSD均<2.0%。结论 该方法操作简便、专属性强，试剂成本低廉、易得，结果准确性高、重复性好，可用于佐芬普利钙中间体(S)-(-)-3-苯甲酰巯基-2-甲基丙酸光学杂质的含量测定。

Abstract:

OBJECTIVE To establish a method for the quantitative determination of optical isomer impurity in the intermediate of zofenopril calcium by GC with pre-column derivatization. METHODS Using D-(+)-2-Octanol as pre-column derivatization reagent, the optimal chromatographic separation was performed on Agilent DB-1701(30 m×0.53 mm, 1.0 μm) column with nitrogen as the carrier gas at a flow rate of 2.0 mL·min^-1, the detector temperature was at 250 ℃, the inlet temperature was at 200 ℃. The temperature program was used. The injection volume was 1.0 μL. RESULTS The calibration curve was good linear relationship in the range of 3.22-121.44 μg·mL^-1 for the optical isomer impurity (R)-(+)-3-benzoyl thiol-2-methyl propionate(r=0.995 2). The limit of quantification was 3.22 μg·mL^-1. The average recovery was 99.6%-102.4%. The RSD of intra and inter day were <2.0%. CONCLUSION The method is simple, specific and accurate with good repeatability, which can be used for the determination of optical isomer impurity in the intermediate of zofenopril calcium.