LC-MS/MS法测定人血浆中罗哌卡因及代谢物浓度及其药动学研究  

Determination of the human plasma concentrations and pharmacokinetics of ropivacaine and its metabo⁃lites by LC-MS/MS

作　　者：徐嘉浩 徐草梅 谢建芬[1] 汤凌凯 仇澜[2] 胡楠[1] XU Jiahao;XU Caomei;XIE Jianfen;TANG Lingkai;QIU Lan;HU Nan(Department of Pharmacy,the First People’s Hospital of Changzhou/the Third Affiliated Hospital of Soochow University,Jiangsu Changzhou 213003,China;Department of Anaesthesiology,the First People’s Hospital of Changzhou/the Third Affiliated Hospital of Soochow University,Jiangsu Changzhou 213003,China)

机构地区：[1]常州市第一人民医院/苏州大学附属第三医院药学部,江苏常州213003 [2]常州市第一人民医院/苏州大学附属第三医院麻醉科,江苏常州213003

出　　处：《中国医院药学杂志》2025年第7期764-769,共6页Chinese Journal of Hospital Pharmacy

基　　金：江苏省药学会恒瑞医药药学基金项目(编号:H202317);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(编号:CM20223005)。

摘　　要：目的:建立一种测定人血浆中罗哌卡因(ropivacaine,ROP)及其主要代谢物3-羟基罗哌卡因(3-hydroxy-ropivacaine,3-OH ROP)浓度的LC-MS/MS方法,研究ROP及其代谢物3-OH ROP在人体中的药动学特征。方法:使用甲醇蛋白沉淀法对人血浆样品进行前处理,色谱柱采用Phenomenex Kinetex^(®)C_(18)色谱柱(100 mm×3 mm,2.6μm),流动相A为含0.01%甲酸和10 mmol·L^(-1)乙酸铵的水溶液,流动相B为含0.01%甲酸的甲醇溶液。ROP定量离子对为m/z→275.3/126.1,3-OH ROP定量离子对为m/z→291.1/126.1。采用地西泮(diazepam,DIA)为内标,DIA定量离子对为m/z→284.7/153.9。收集行胸腔镜下肺切除术并给予等剂量(3 mg·kg^(–1))的ROP进行超声引导下前锯肌平面阻滞的患者不同时间点的血浆样本,并检测ROP及其代谢物3-OH ROP的血药浓度,计算相应的药动学参数。结果:LC-MS/MS法可同时检测人血浆中ROP及3-OH ROP的浓度,在标准曲线范围(ROP:0.04~4μg·mL^(–1)、3-OH ROP:0.004~0.4μg·mL^(–1))内线性良好;批内和批间精密度5%~10%;准确度89.31%~111.07%;提取回收率85.31%~98.67%;基质效应89.72%~100.74%;稳定性良好。应用本方法检测不同时间点人血浆中ROP及3-OH ROP的血药浓度,并计算药动学参数,结果显示,ROP的达峰时间为(0.58±0.28)h,峰浓度为(1.59±0.39)μg·mL^(–1)及清除率为(210.30±99.40)mL·h^(–1)·kg^(–1),3-OH ROP的达峰时间为(1.25±0.54)h,峰浓度为(0.07±0.01)μg·mL^(–1)及清除率为(3079±1366)mL·h^(–1)·kg^(–1)。结论:该法准确、灵敏,操作简单,特异性强,适用于临床ROP及其主要代谢物3-OH ROP的血药浓度监测以及药动学研究。OBJECTIVE To create a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method to determine the human plasma concentrations of ropivacaine(ROP)and its major metabolite 3-hydroxy-ropivacaine(3-OH ROP),aiming to investigate the pharmacokinetic characteristics of ROP and its metabolite 3-OH ROP in the human body.METHODS Human plasma samples were precipitated with methanol,and a Phenomenex Kinetex^(®)C_(18)column(100 mm×3 mm,2.6μm)was used for chromatography.The mobile phase A was a solution of water containing 0.01%formic acid and 10 mmol·L^(-1)ammonium acetate,while the mobile phase B was a methanol solution containing 0.01%formic acid.The quantification ion pair was m/z→275.3/126.1 for ROP,and m/z→291.1/126.1 for 3-OH ROP.Diazepam(DIA)was used as an internal standard,and the quantitative ion pair of DIA was m/z→284.7/153.9.Blood samples were collected from patients undergoing video-assisted thoracoscopic lung resection who received an equal dose(3 mg·kg^(-1))of ROP for ultrasound-guided subcostal plane block.Plasma concentrations of ROP and its metabolite 3-OH ROP were measured at different time points,and corresponding pharmacokinetic parameters were analyzed.RESULTS The LC-MS/MS method could simultaneously detect the concentrations of ROP and its metabolite 3-OH ROP in human plasma,with good linearity within the standard curve range(ROP:0.04-4μg·mL^(-1),3-OH ROP:0.004-0.4μg·mL^(-1)).The intra-and inter-batch precision was 5%-10%;accuracy was between 89.31%and 111.07%;extraction recovery was in the range of 85.31%-98.67%;matrix effect was between 89.72%and 100.74%;and stability was good.Plasma concentrations and pharmacokinetic parameters of ROP and 3-OH ROP at different time points detected by LC-MS/MS showed that the time to peak concentration,peak concentration,and clearance rate of ROP were(0.58±0.28)h,(1.59±0.39)μg·mL^(-1),and(210.30±99.40)mL·h^(-1)·kg^(-1),respectively;and(1.25±0.54)h,(0.07±0.01)μg·mL^(-1),and 3079±1366 mL·h^(-1)·kg^(-1)for 3-OH ROP,respectively.CONCLUSION

关 键 词：罗哌卡因 3-羟基罗哌卡因 液相色谱-串联质谱法 血药浓度 药动学 

分 类 号：R969[医药卫生—药理学]