LC-MS/MS测定硫酸氢氯吡格雷中的痕量四乙基溴化铵

Determination of Residual Tetraethyl Ammonium Bromide in Clopidogrel Sulfate by LC-MS/MS

目的建立LC-MS/MS测定硫酸氢氯吡格雷中的痕量四乙基溴化铵。方法采用Waters Atantis HILIC silica色谱柱(2.1 mm×100 mm,5μm),以甲酸铵缓冲液(0.05 mol·L^(-1)甲酸铵的0.1%甲酸溶液)-乙腈(15︰85)为流动相,流速为0.2 mL·min^(-1),柱温35℃,进样体积1μL。采用三重四级杆质谱仪在正离子模式下多反应监测(MRM)模式对硫酸氢氯吡格雷中的四乙基溴化铵进行定量检测。结果四乙基溴化铵在0.005 0~1.993 3μg·mL^(-1)内线性关系良好(r=0.999 8),加标回收率为94.9%(n=9),重复性RSD为1.8%,定量限为0.14 ng·mL^(-1)。6批样品中四乙基溴化铵均未超出检出限。结论本方法准确、快速、灵敏、重复性好,适用于硫酸氢氯吡格雷中的痕量四乙基溴化铵的测定。

OBJECTIVE To develop an LC-MS/MS method for the determination of residual tetraethyl ammonium bromide in clopidogrel sulfate. METHODS The separation was performed on a Waters Atantis HILIC silica column（2.1 mm× 100 mm, 5 μm）, the mobile phase was the 0.1% formic acid solution of 0.05 mol·L-1 ammonium formate -acetonitril（15：85） at the flow rate of 0.2 mL·min-1, the column temperature was 35℃ and the sample volume was 1μL. The detection of tetraethyl ammonium bromide in clopidogrel sulfate was achieved by triple quadrupole mass spectrometry with positive ionization using MRM mode. RESULTS The calibration curve was linear in the range of 0.005 0-1.993 3 μg.mL-1 （r=0.999 8）, the average recovery was 94.9%（n=9）, RSD of repeatability was 1.8%, the LOQ was 0.14 ng.mL-1. The residual tetraethyl ammonium bromide were less than LOD in 6 batches of samples. CONCLUSION The method is accurate, rapid, sensitive, and reproducible to determine the residual tetraethyl ammonium bromide in clopidogrel sulfate.