LC-MS/MS法测定人血浆中氯马斯汀浓度

LC-MS/MS determination of clemastine concentration in human plasma

目的:建立LC-MS/MS法测定人血浆中氯马斯汀浓度,并进行其药代动力学和生物等效性研究。方法:血浆样品以苯海拉明为内标,经提取溶剂[正己烷-二氯甲烷-异丙醇(30∶20∶1)]萃取后进行LC-MS/MS分析。采用高效液相色谱分离系统,色谱柱为Inertsil Hilic C18柱(150 mm×3.0 mm,5μm),流动相为乙腈10 mmo·lL-1醋酸铵溶液)-甲酸(40∶60∶1)。采用质谱检测系统,ESI离子源,正离子模式,多级反应监测(MRM)方式,m/z344→215(氯马斯汀),m/z256→167(内标,苯海拉明)。结果:在0.01～5.0 ng·mL-1范围内,氯马斯汀血药浓度呈良好的线性关系(r=0.9972),精密度RSD%均小于10%,准确度在90.8%～102%。结论:本测定方法灵敏准确,适用于人血浆中氯马斯汀浓度的测定。

Objective：To develop a sensitive and selective LC-MS/MS method to quantitate clemastine in human plasma and study the pharmacokinetic and bioequiavailability of clemastine in healthy volunteers after a single dose of 1.34 mg clemastine fumarat tablet.Method：After adding diphenhydramine as the internal standard,clemastine was extracted from plasma by extraction solvent [N-hexane-dichlormethane-dimethyl carbinol（30∶ 20∶ 1）].The analyte was isocratically eluted on a Inertsil Hilic C18 column（150 mm×3.0 mm,5 μm） with acetonitrile-water（10 mmol·L-1 ammonium acetate）-formic acid（40∶ 60∶ 1） by LC-MS/MS with positive ionization.Ions monitored in the multiple reaction monitoring（MRM） mode were m/z 344→215 for clemastine and m/z 256→167 for diphenhydramine（IS）.Result：The linear range of the standard curve of clemastine was from 0.01 to 5.0 ng·mL-1.RSD of precision was less than 10%,and the accuracy was between 90.8%-102%.Conclusion：The method is highly sensitive and accurate,which is suitable for the pharmacokinetic study of clemastine.