GC-MS测定硫酸氢氯吡格雷中硫酸二甲酯的残留量

Trace Determination of Dimethyl sulfate in Clopidogrel bisulfate by GC-MS

关键词:  硫酸氢氯吡格雷  硫酸二甲酯  甲基化  顶空气相色谱-质谱联用

Key words:  clopidogrel bisulfate  dimethyl sulfate  methylation  HS-GC-MS

摘要:

目的 采用顶空气相色谱-质谱联用法(HS-QC-MS)测定硫酸氢氯吡格雷中硫酸二甲酯杂质的含量。方法 选用DB-624毛细管柱(30 m×0.32 mm，1.5 μm)，程序升温，初始温度为40 ℃，保持8 min，以30 ℃·min^–1升到220 ℃，保持2 min，以氦气为载气，流速为2.0 mL·min^–1，采用电子轰击电离(EI)源，在选择离子监测模式下选择m/z 45，56，88进行检测。结果 硫酸二甲酯浓度在0.15~3.0 μg·mL^–1内与峰面积线性关系良好(r²=0.994 2)；检测限为0.05 μg·mL^–1，定量限为0.15 μg·mL^–1；杂质硫酸二甲酯平均回收率为83.9%，RSD(n=9)为4.0%。经检测，硫酸氢氯吡格雷样品中硫酸二甲酯有少量检出。结论 本方法操作简便，结果准确，灵敏度高，可用于硫酸氢氯吡格雷样品中硫酸二甲酯的测定。

Abstract:

OBJECTIVE To establish a head space gas chromatography mass spectrometry(HS-GC-MS) analytical method for the trace determination of dimethyl sulfate in clopidogrel bisulfate. METHODS The analytical column was DB-624(30 m×0.32 mm, 1.5 μm). The column temperature was maintained at 40℃, holding for 8 min, then was raised to 220℃ at the rate of 30℃·min^-1, holding for 2 min. The flow rate of carrier gas helium was 2.0 mL·min^-1. The detection was achieved in electron impact ionization(EI), and the selected ions were m/z 45, 56 and 88 in the selected ion monitoring mode. RESULTS The calibration curve of dimethyl sulfate was in a good linearity over the range of 0.15-3.0 μg·mL^-1(r²=0.994 2). The limit of detection was 0.05 μg·mL^-1, and the limit of quantification was 0.15 μg·mL^-1. The average recovery of dimethyl sulfate was 83.9%, and the RSD(n=9) was 4.0%. There was a little of dimethyl sulfate detected in one batch of clopidogrel bisulfate sample. CONCLUSION The method is easy to operate, accurate in results and high in sensitivity, which is applicable for the quality control of dimethyl sulfate in clopidogrel bisulfate.