LC-MS/MS法测定人体利多卡因浓度及药代动力学的应用

LC-MS/MS determination of lidocaine in human plasma and application in pharmacology

目的:建立LC-MS/MS法测定人体血浆利多卡因的浓度,并研究NAL1282利多卡因贴剂(5%)的药代动力学。方法:色谱柱为YMC C18(150 mm×2.1 mm,5μm),流动相为乙腈-20 mmol·L-1甲酸铵(87:13,v/v);流速:0.25 mL·min-1;进样量:5μL;柱温:40℃,样品室温度为15℃。采用随机、单剂量给药、开放性、两周期交叉设计的单中心试验,分别给予9名健康受试者NAL1282利多卡因贴剂3贴,700 mg·贴-1。采用LC-MS/MS法测定给药后不同时间的血药浓度。结果:利多卡因线性范围为0.8～206 ng·mL-1,最低检测限为0.2 ng·mL-1,方法灵敏、稳定、特异性高。利多卡因贴剂主要药代动力学参数Cmax、Tmax、AUC0→24和AUC0→∞分别为(61.6±18.5)ng·mL-1;9 h(6 h,12 h);(848.4±231.7)ng·h·mL-1;(1129.3±324.0)ng·h·mL-1。结论:该方法简便、准确,重复性好,并可应用到人体利多卡因贴剂药代动力学的研究。

Objective：To establish an LC-MS/MS method for determination of lidocaine in human plasma,and to study the pharmacokinetics of NAL1282 lidocaine patch（5%）.Methods：YMC C18 column（150 mm×2.1 mm,5 μm） was adopted in the experiment.The column temperature was set at 40 ℃,acetonitrile-20 mmol·L-1 ammonium（87：13,v/v）was used as mobile phase at the flow rate of 0.25 mL·min-1.The sample room temperature was set at 15 ℃ and the injection volume was 5 μL.It was a randomized,single dose,open,two-period crossover and single-center trial design,9 healthy subjects were given lidocaine patch NAL1282 of 3 patches,700 mg per patch,and the blood concentration were determined by LC-MS/MS at different times after administration.Results：Lidocaine was linear range of 0.8-206 ng·mL-1,the limitation of detection for lidocaine was about 0.2 ng·mL-1,the method was high sensitivity,stability and specificity and has been used for pharmacokinetics study of lidocaine in vivo successfully.The main pharmacokinetic parameters of lidocaine patch were as follows：Cmax、Tmax、AUC0→6and AUC0→∞（mean±standard deviation） were（61.6±18.5） ng·mL-1;9 h（6 h,12 h）;（848.4±231.7） ng·h·mL-1;（1129.3±324.0） ng·h·mL-1,respectively.Conclusion：The method is simple,accurate and repetitive for the determination of lidocaine in human plasma,and successfully applied to the human pharmacokinetics study of lidocaine patch.