LC-MS／MS法测定右溴苯那敏的血药浓度及其药动学特征评价

目的建立液相色谱-串联质谱（LC-MS/MS）法测定人血浆中右溴苯那敏的浓度，并评价右溴苯那敏在健康受试者体内的药动学特征。方法血浆经参有氯苯那敏为内标的甲醇沉淀后在Inertsil ODS-3柱（150mm×2．1mm，5μm）上分离，流动相采用含10mmol·L^-1甲酸铵的甲醇／sic／甲酸（60：40：0．1，V／V／V）溶液。串联质谱sciex API 3000采用正电喷雾离子源和多反应监测的扫描模式。结果右溴苯那敏在0．1—40μg·L^-1内线性良好，定量下限为0．1μg·L^-1。方法的准确度为87％～113％，批内、批间的RSD均〈15％。右溴苯那敏的主要药动学参数ρmax、tmax、t1/2、AUC0→t。和AUC0→∞在单剂量给药后分别为：（3．58±1．14）μg·L^-1、（9．42±2．94）h、（18．46±9．48）h、（108．4±53．97）μg·L^-1和（126．3±73．91）μg·L^-1；在多剂量给药后分别为：（14．59±6．75）μg·L^-1,（6．35±2．09）h、（21．40±7．74）h、（487．9±316．2）μg·L^-1和（578．0±437．3）μg·L^-1。稳态时的药动学参数AUC^88、ρmax、tmax和DF分别为：（153．0±74．47）μg·L^-1、（12．07±5．84）μg·L^-1、（12．75±6．21）μg·L^-1和（21．2±7．7）％。结论本方法专属性强，精确，灵敏度高，操作简单，快速。结果表明单剂量和多剂量给药后ρmax、tmax和AUC^88之间的差异有统计学意义，右溴苯那敏在体内有蓄积。

Dexbrompheniramine determination and pharmacokinetics in human plasma using LC-MS/MS

AIM To develop a LC-MS/MS method for determining dexbrompheniramine （DBP） in hmnan plasma and evaluate the pharmacokinetics of DBP in Chinese healthy subjects after a single and multiple oral doses. METHODS Plasma samples were pretreated by methanol spiked with chlompheniramine as internal standard, then separated by chromatography on an Inertsil ODS-3 column （ 150 mm × 2.1 mm, 5 μm） using a mobile phase consisted of methanol- water-formic acid （60：40：0.1, V/V/V） containing 10 mmol· L^-1 ammonium formate. Detection was carried out on a Sciex API 3000 using positive electrospray ion source and multiple reaction monitoring scan mode. RESULTS The linear calibration curve was in a range of 0.1 - 40μg· L^- 1 with a limit of quantitation of 0.1μg· L^- 1. The accuracy was within 87 % - 113 % and the relative standard deviation （RSD） of inter-batch and intra-batch precision was less than 15%. The main phannacokinetic parameters ρmax, tmax, t1/2, AUC0-1 and AUC0-∞ were （3.58± 1.14）pg·L^-1, （9.42 ± 2.94）h, （18.46 ± 9.48）h, （108.4 ± 53.97） pg·h·L^-1 and （126.3 ± 73.91） pg·h·L^-1 after a single dose and （14.59 ± 6.75）pg·h·L^-1, （6.35 ± 2.09）h, （21.40± 7.74）h, （487.9 ±316.2）pg·h·L^-1 and （578.0 ±437.3）pg·h·L^-1 after multiple doses, respectively. The steady-state pharmacokinetic parameters AUC^88, Pain, Pay and DF were （153.0 ± 74.47）μg·L^-1, （12.07 ＋ 5.84）μg·L^-1, （12.75 ± 6.21）μg·L^-1 and （21.2± 7.7）%, respectively. CONCLUSION The method is specific, simple, rapid, precise, accurate and sensitive. Statistical analysis shows sig- nificant differences in ρmax, tmax and AUC0-1 between single and multiple doses administration. There is accumulation of DBP after multiple doses.