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目的建立测定大鼠血浆和尿液中枸地氯雷他定的液相色谱-串联质谱(LC-MS/MS)法,并将其应用于枸地氯雷他定在大鼠体内的药动学研究。方法 12只成年健康SD大鼠,随机分成两组,各6只,分别单剂量尾静脉注射枸地氯雷他定0.5 mg·kg-1和灌胃枸地氯雷他定2 mg·kg-1后,于一定时间点采集血浆或尿液,取生物样品50μL经液液萃取后,以甲醇-0.1%甲酸水溶液(70∶30,V/V)为流动相,选用Diamonsil 5u C18色谱柱(4.6 mm×100 mm,5μm)分离,采用电喷雾离子化进行正离子检测。用于定量分析的离子反应分别为m/z 311→259(枸地氯雷他定)和m/z 327→270(氯氮平)。使用Win Nonlin软件计算药动学参数。结果单剂量静脉注射枸地氯雷他定0.5 mg·kg-1和单剂量灌胃枸地氯雷他定2 mg·kg-1的主要药动学参数:ρmax分别为(457.00±49.76)和(17.25±4.09)μg·L-1,AUC0-∞分别为(128.80±19.40)和(107.38±10.74)μg·h·L-1,t1/2分别为(3.47±0.27)和(5.33±0.22)h,MRT分别为(4.19±0.62)和(7.22±0.39)h,绝对生物利用度为20.86%;0~72 h的尿药累积排泄率分别为(1.19±0.21)%和(0.38±0.11)%。结论建立的液质联用测定枸地氯雷他定在血浆和尿液样品的方法 ,专属灵敏快速,适用于大鼠药动学研究。
Objective To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of desloratadine in plasma and urine of rats, and apply it to the pharmacokinetics of desloratadine in rats Study. Methods Twelve adult healthy SD rats were randomly divided into two groups with 6 rats in each group. Single dose of desloratadine 0.5 mg · kg-1 and gavage desloratadine 2 mg · kg- 1, plasma or urine was collected at a certain time point. 50μL of biological sample was extracted by liquid-liquid extraction, and then eluted with methanol-0.1% formic acid aqueous solution (70:30, V / V) as mobile phase. Diamonsil 5u C18 column 4.6 mm × 100 mm, 5 μm), positive ion detection was performed using electrospray ionization. The ion reactions used for the quantitative analysis were m / z 311 → 259 (loratadine) and m / z 327 → 270 (clozapine), respectively. Pharmacokinetic parameters were calculated using Win Nonlin software. Results The main pharmacokinetic parameters of single dose intravenous desloratadine 0.5 mg · kg-1 and single dose oral desloratadine 2 mg · kg-1: ρmax were (457.00 ± 49.76) and (17.25 ± 4.09) μg · L-1, and the AUC0-∞ were (128.80 ± 19.40) and (107.38 ± 10.74) μg · h · L-1, t1 / 2 were (3.47 ± 0.27) and (5.33 ± 0.22 ) h and MRT were (4.19 ± 0.62) and (7.22 ± 0.39) h respectively, with an absolute bioavailability of 20.86%. Urine cumulative excretion rates at 0 ~ 72 h were (1.19 ± 0.21)% and (0.38 ± 0.11) )%. Conclusion The established method of LC-MS for the determination of desloratadine in plasma and urine samples is sensitive and rapid and is suitable for pharmacokinetic studies in rats.