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目的建立人血浆和尿样中阿德福韦浓度的液相色谱-串联质谱(LC-MS/MS)测定方法。方法10名健康受试者单剂量口服阿德福韦10mg。于服药前(0h)和服药后抽取静脉血及留取尿样。采用BDS-Phenyl column(250mm×4.6mm,5μm)色谱柱,流动相为甲醇-0.35mol·L-1冰醋酸梯度洗脱,流速为0.3mL.min-1;电喷雾离子化正离子选择性反应检测;检测离子为m/z274.1→162.1(阿德福韦),m/z254.1→135.0(喷昔洛韦,内标)。结果LC-MS/MS测定阿德福韦血浆样品线性范围为0.50~200μg.L-1,尿样线性范围为50~20000μg·L-1,线性关系良好。血浆样品分析的回收率、精密度和准确度均良好,定量限为0.50μg·L-1。主要药动学参数为:ρmax(24±s4)μg·L-1,tmax(1.0±0.6)h,AUC0~t(278±45)h.μg·L-1,AUC0~∞(285±45)h.μg·L-1,t1/2(8.8±1.6)h,CL(F)(36±6)L.h-1,Vd(F)(456±136)L,0~48h的尿累计排泄量为(48±12)%。结论建立的LC-MS/MS测定法专属性强、灵敏度适宜,可以用于阿德福韦的药动学研究。
Objective To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of adefovir concentration in human plasma and urine samples. Methods Ten healthy volunteers received a single oral dose of adefovir 10 mg. Before medication (0h) and after taking the venous blood and urine samples. The mobile phase was eluted with a gradient of methanol-0.35 mol·L-1 glacial acetic acid at a flow rate of 0.3 mL · min-1 using a BDS-Phenyl column (250 mm × 4.6 mm, 5 μm). The electrospray ionization positive ion selectivity Reaction detection; detection ion m / z274.1 → 162.1 (adefovir), m / z254.1 → 135.0 (penciclovir, internal standard). Results The linear range of adefovir plasma was 0.50 ~ 200μg.L-1 and the linear range of urine samples was 50 ~ 20000μg · L-1 by LC-MS / MS. The linearity was good. The recovery, precision and accuracy of plasma samples were good, with a limit of quantification of 0.50μg · L-1. The main pharmacokinetic parameters were ρmax (24 ± s4) μg · L-1, tmax (1.0 ± 0.6) h, AUC0 ~ t (278 ± 45) h.μg · L-1 and AUC0 ~ ∞ ) cumulative excretion of urine in h.μg · L-1, t1 / 2 (8.8 ± 1.6) h, CL (F) (36 ± 6) Lh-1, Vd (F) (456 ± 136) L, The amount of (48 ± 12)%. Conclusion The established LC-MS / MS assay is specific and sensitive and can be used for pharmacokinetics studies of adefovir.