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目的建立测定人血浆和尿液中培拉米韦的LC-MS/MS法。方法 12名中国健康受试者单次静脉滴注培拉米韦三水合物氯化钠注射液,给药剂量为600 mg,采集血浆样本和尿液样本并测定其中培拉米韦的浓度。血浆样本以乙腈沉淀蛋白、尿液样本经直接稀释后,选用Synergi Hydro-RP 80A C18色谱柱(150 mm×2.0 mm,4μm),以甲醇︰0.5%甲酸=35︰65(V/V)为流动相,流速为0.4 m L·min-1。选用三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,正离子方式。使用Win Nonlin 6.3软件计算药动学参数。结果血浆和尿液中培拉米韦的线性范围分别为0.024 0~60.0 mg·L-1、0.400~1 000 mg·L-1;测定血浆中培拉米韦的日内、日间相对标准差(RSD)均小于8.0%,相对误差(RE)在±8.0%的范围以内,测定尿液中培拉米韦的日内、日间RSD均小于4.0%,RE在±10.0%的范围以内;提取回收率较高,且可重现;血浆和尿液样本中的内源性物质不干扰培拉米韦和内标的测定;培拉米韦在各种贮存条件下均较稳定。中国健康受试者单次静脉滴注培拉米韦600 mg后的主要药动学参数如下:ρmax为(41.1±5.3)mg·L-1,AUC0-t为(112.1±13.2)mg·h·L-1,AUC0-∞为(112.3±13.2)mg·h·L-1,t1/2为(3.28±1.15)h。36 h内,培拉米韦的尿液累积排泄率为(90.50±7.38)%。结论该方法快速、灵敏、专属性强、重现性好,适用于培拉米韦的人体药动学研究。
Objective To establish a LC-MS / MS method for the determination of peramivir in human plasma and urine. Methods Twelve Chinese healthy subjects received a single intravenous infusion of peramivir sodium chloride trihydrate intravenous injection at a dose of 600 mg. Plasma samples and urine samples were collected and the concentration of peramivir was determined. The plasma sample was precipitated with acetonitrile and the urine sample was diluted directly on a Synergi Hydro-RP 80A C18 column (150 mm × 2.0 mm, 4 μm) with methanol: 0.5% formic acid = 35: 65 (V / V) Mobile phase with a flow rate of 0.4 m L · min-1. Multi-reaction monitoring (MRM) scanning with triple quadrupole mass spectrometer was used for monitoring, electrospray ionization source and positive ion mode. Pharmacokinetic parameters were calculated using Win Nonlin 6.3 software. Results The linear range of peramivir in plasma and urine was 0.024 0-60.0 mg · L-1 and 0.400-1000 mg · L-1, respectively. The relative standard deviations (RSD) were less than 8.0% and the relative error (RE) was within ± 8.0%, RSDs of urine and urine were less than 4.0% and RE within ± 10.0% The recovery is high and reproducible; the endogenous substances in the plasma and urine samples do not interfere with the determination of beramirvir and the internal standard; peramivir is more stable under all storage conditions. The main pharmacokinetic parameters of peramivir 600 mg in Chinese healthy subjects were as follows: ρmax was (41.1 ± 5.3) mg · L-1, and AUC0-t was (112.1 ± 13.2) mg · h · L-1, AUC0-∞ of (112.3 ± 13.2) mg · h · L-1 and t1 / 2 of (3.28 ± 1.15) h. Within 36 h, the urine excretion rate of peramivir was (90.50 ± 7.38)%. Conclusion The method is rapid, sensitive, specific and reproducible. It is suitable for the study of peramivir in human pharmacokinetics.