基于LC-MS/MS方法的大鼠血浆中舒必利的血药浓度检测及药代动力学研究  

Determination of sulpiride concentration in rat plasma and pharmacokinetics by LC-MS/MS

作　　者：梁媛 葛若衡 舒畅[1,2] LIANG Yuan;GE Ruo-heng;SHU Chang(Key Laboratory of Drug Quality Control and Pharmacovigilance in China Pharmaceutical University,Ministry of Education,Nanjing 210009;Department of Pharmaceutical Analysis,School of Pharmacy,China Pharmaceutical University,Nanjing 211198)

机构地区：[1]中国药科大学药品质量控制与药物警戒教育部重点实验室,南京210009 [2]中国药科大学药学院药物分析系,南京211198

出　　处：《中南药学》2023年第11期2875-2879,共5页Central South Pharmacy

基　　金：药物质量与安全预警教育部重点实验室资助项目(No.DQCP20/21PQ02);江苏省特色资源开发与药用研究重点实验室(No.LPRK202102)。

摘　　要：目的建立一种LC-MS/MS方法用于大鼠血浆中舒必利血药浓度的测定及其药代动力学研究。方法血浆样本经过液液萃取方法处理后,采用电喷雾离子化(ESI),正离子多重反应监测模式(MRM)。舒必利和奥美拉唑用于定量分析的离子对为m/z 342.2→112.2和346.4→198.1。色谱柱为Hedera ODS-2柱(150 mm×2.1 mm,5μm),流动相是甲醇(含0.1%甲酸)-水(0.05%甲酸铵和0.1%甲酸),按照等度洗脱方式(7∶3,V/V)进行。结果该方法的定量下限是0.5 ng·mL^(-1),舒必利在0.5~200 ng·mL^(-1)内与峰面积比值线性关系良好,舒必利和内标奥美拉唑的提取回收率在70%~80%,批间和批内精密度均小于15%,方法学验证的结果符合生物样本分析指导原则要求。结论建立的LC-MS/MS方法特异性强,分析时间短,适用于大量生物样本的检测,成功应用于大鼠血浆样本的药代动力学研究,可为舒必利的临床药物浓度监测方法的开发提供参考。Objective To monitor the concentration of sulpiride in the plasma,and to conduct its pharmacokinetic by LC-MS/MS.Methods Plasma samples were collected by liquid-liquid extraction method.Sulpiride and omeprazole for quantitative analysis were m/z 342.2→112.2 and 346.4→198.1.The determination was performed on Hedera ODS-2 column(150 mm×2.1 mm,5μm).The mobile phase was methanol(containing 0.1%formic acid)and water(0.05%ammonium formate and 0.1%formic acid)=(7∶3,V/V).Results The lower limit of quantification of the method was 0.5 ng·mL^(-1),and the linearity was good at 0.5~200 ng·mL^(-1).The extraction recovery of sulpiride and internal standard omeprazole ranged 70%~80%,and the RSD were less than 15%.The methodology verification was in line with the requirements of guidelines for biological sample analysis.Conclusion The LC-MS/MS method is suitable for the detection of large biological samples.It has been successfully used in the pharmacokinetic study and concentration monitoring of sulpiride.

关 键 词：舒必利 LC-MS/MS 药代动力学 血药浓度 

分 类 号：R969.1[医药卫生—药理学]