LC-MS/MS法测定大鼠血浆中亚胺培南浓度及其药动学研究  

Determination of Plasma Imipenem and Its Pharmacokientics in Rats by LC-MS/MS

作　　者：钱敏燕 杨旭萍 蒋振伟 左李安 胡楠[1] 王莉英 QIAN Minyan;YANG Xuping;JIANG Zhenwei;ZUO Li'an;HU Nan;WANG Liying(Department of Pharmacy,the Third Affiliated Hospital of Soochow University/Changzhou First People's Hospital,Changzhou 213003,China)

机构地区：[1]苏州大学第三附属医院/常州市第一人民医院药学部,常州213003

出　　处：《药学与临床研究》2023年第2期119-123,共5页Pharmaceutical and Clinical Research

基　　金：常州市科技基础设施建设计划-常州市临床药学重点实验室(CM20223005)。

摘　　要：目的:建立了一种测定大鼠血浆中亚胺培南(IMP)浓度的LC-MS/MS方法,研究不同剂量的IMP在SD大鼠中的药代动力学特征。方法:大鼠血浆样品使用乙腈蛋白沉淀,色谱柱采用Phenomenex Kinetex@HILIC柱(50 mm×2.1 mm,2.6μm),流动相为0.1%甲酸水溶液(含5 mmol·L^(-1)乙酸铵)-乙腈,行梯度洗脱。采用电喷雾离子源(ESI),正离子多反应监测模式(MRM),IMP定量离子对为m/z 300.0→m/z 142.0。大鼠腹腔注射IMP(50、100和200 mg·kg^(-1))后于不同时间采血并检测其血药浓度,计算药代动力学参数。结果:测定血浆中IMP的线性范围为0.20~200μg·mL-1,日内及日间精密度(RSD)均<11.46%,准确度为91.67%~105.38%,基质效应为91.33%~104.63%,回收率为88.90%~101.55%,均符合生物样品的分析要求。大鼠腹腔注射50、100和200 mg·kg^(-1)IMP后主要药动学参数Cmax分别为(86.15±31.59)、(165.59±23.57)和(322.32±63.97)μg·mL^(-1);t1/2分别为(26.31±6.87)、(29.90±2.27)和(49.71±5.25)min;AUC0-∞分别为(5261.40±1513.08)、(13803.56±1308.5)和(36412.38±6309.41)μg·min^(-1)·mL^(-1)。结论:本法准确、灵敏,适用于大鼠腹腔注射不同剂量IMP后的浓度检测及药代动力学研究。Objective:To establish an LC-MS/MS method for detecting imipenem(IMP)in rat plasma and to study the pharmacokinetic characteristics of imipenem in rats.Methods:Plasma samples of IMP were treated for protein precipitation with acetonitrile.The samples were separated with a Phenomenex Kinetex@HILIC column(50 mm×2.1 mm,2.6μm)under gradient elution with the mobile phase consisted of 0.1%formic acid aqueous solution(containing 5 mmol·L^(-1)ammonium acetate)-acetonitrile.The analytes were monitored in multiple reaction monitoring modes(MRM)by positive electrospray ionization(ESI).The mass transition pairs were m/z 300.0→m/z 142.0 for imipenem.After intraperitoneal injection of IMP(50,100,and 200 mg·kg^(-1)),blood samples were collected at each time points and the plasma concentrations of IMP were detected to calculate the pharmacokinetic parameters.Results:The linear range of IMP standard curves was 0.2-200μg·mL^(-1),the intra-and inter-day precisions(RSD)were all below 11.46%,the accuracy were 91.67%-105.38%,the matrix effects were 91.33%-104.63%,and the recoveries were 88.90%-101.55%,which were all in line with the analysis requirements of biological samples.For the main pharmacokinetic parameters of IMP at 50,100,and 200 mg·kg^(-1),Cmax were(86.15±31.59),(165.59±23.57)and(322.32±63.97)μg·mL^(-1),t1/2 were(26.31±6.87),(29.90±2.27)and(49.71±5.25)min,AUC0-∞were(5261.40±1513.08),(13803.56±1308.55)and(36412.38±6309.41)μg·min^(-1)·mL^(-1),respectively.Conclusion:This method is accurate,sensitive,and has been successfully applied to detecting IMP in rat plasma and to the pharmacokinetic study of imipenem intraperitoneal injections at different doses.

关 键 词：亚胺培南 液相色谱串联质谱 大鼠 药代动力学 

分 类 号：R969.1[医药卫生—药理学]