帕拉米韦三水合物注射液在人体的药代动力学分析

The Pharmacokinetic Study of Peramivir Trihydrate in Healthy Volunteers

目的研究帕拉米韦三水合物注射液在健康志愿者的药代动力学试验。采用液相串联质谱联用法(LC-MS/MS)对待测生物样品进行分析,测定主要成分帕拉米韦的血药浓度,估算其主要药代动力学参数,了解帕拉米韦三水合物注射液在健康人体内的吸收,为制定帕拉米韦三水合物注射液的临床试验方案提供试验依据,同时也为临床用药的给药剂量提供依据。方法采用Agilent Eclipse Plus C18色谱柱(4.6mm×100mm,5μm),甲醇∶水(0.1%甲酸、0.06mmol·L^-1甲酸铵)70∶30(V/V)为流动相等度洗脱,流速为0.5mL·min^-1,柱温35℃。采用多重反应监测(MRM)帕拉米韦(m/z329.0→270.0)和内标氘代帕拉米韦(m/z332.1→273.1)的测定。结果帕拉米韦的线性范围为5~10000ng·mL^-1。其相关系数r2=0.9921,定量下限为5ng·mL^-1,批内和批间的RSD分别为3.61%和4.08%以内,准确度在95.75%~106.42%之间。结论该方法灵敏、快速、简单、准确,可用于帕拉米韦的临床血药浓度监测和药代动力学研究。

OBJECTIVE To study the pharmacokinetics of peramivir trihydrate inject-ion in health volunteers.A liquid chromatography tandem mass spectrometry method(LC-MS/MS)was used to investigate the pharmacokinetic profiles of peramivir after Intravenous injection in healthy volunteers.The calculated concentrations and parameters helped to understand absorption of peramivir in human,provide fundamentaldata for clinical trialsearch and clinical application.METHODS Peramivir was extracted with methanol and the residues were analyzed by a LC-MS/MS system(Agilent Eclipse Plus C 18 column,4.6mm×1 00mm,5μm)with the mobile phase consisted of methanol(0.1%formic acid)and 0.06mmol·L-1 ammonium formate 70∶30(V/V),with a flow rate of 0.5mL·min^-1 and temperature of 35℃.Multiple reaction monitoring(MRM)using the precursor to production combinations of m/z 329.0→270.0 and m/z 332.1→273.1 was performed to detect peramivir and the inter-nal standard,respectively.RESULTS The method was linear over a concentration range of 5-10000ng·mL^-1.The LLOQ was 5ng·Ml^-1.The average inter-day/intra-day precision values ranged from 3.61%to 4.08%,respectively,while the accuracy values ranged from 95.75%to 106.42%.CONCLUSION The method provides a sensitive,accurate,simple and rapid,and reliable analytical procedure for clinical monitoring of perami-vir plasma and its pharmacokinetic studies.