LC-MS/MS法测定人体利多卡因浓度及药代动力学的应用

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,5 μm),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:5 μL;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C_max、T_max、AUC_0→24和AUC_0→∞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:C_max、T_max、AUC_0→6and AUC_0→∞(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.