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目的建立人血浆中氯沙坦钾及其活性代谢物5-羧酸氯沙坦(EXP-3174)和氢氯噻嗪浓度的液相色谱-串联质谱(LC-MS/MS)测定法,研究氯沙坦钾氢氯噻嗪片在健康人体内的药动学。方法 24名男性健康受试者单剂量空腹口服氯沙坦钾氢氯噻嗪片后48 h内间隔采集肘静脉血,分离血浆测定氯沙坦钾,EXP-3174和氢氯噻嗪血药浓度,采用DAS2.0软件计算药动学参数。结果氯沙坦钾、EXP-3174和氢氯噻嗪的主要药动学参数ρmax分别为(276±127)、(463±135)和(63.8±19.2)μg·L-1;tmax分别为(1.43±1.06)、(3.67±1.32)和(2.40±0.79)h;t1/2分别为(1.53±0.44)、(4.72±1.27)和(5.77±1.52)h;AUC0-48分别为(505±120)、(3 305±646)和(415±103)μg·h·L-1。结论建立的LC-MS/MS测定法专属准确、灵敏度高,可用于氯沙坦钾氢氯噻嗪片血药浓度分析及药动学研究。
OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of losartan potassium and its active metabolites losartan-5-carboxylate (EXP- 3174) and hydrochlorothiazide in human plasma. Pharmacokinetics of potassium hydrochlorothiazide tablets in healthy volunteers. Methods Twenty-four male healthy subjects were given bolus fasting serum losartan potassium hydrochlorothiazide tablets within 48 h after the interval to collect elbow venous blood, plasma concentrations of losartan potassium, EXP-3174 and hydrochlorothiazide plasma concentrations were determined using DAS2.0 software Pharmacokinetic parameters were calculated. Results The main pharmacokinetic parameters ρmax of losartan potassium, EXP-3174 and hydrochlorothiazide were (276 ± 127), (463 ± 135) and (63.8 ± 19.2) μg · L-1, respectively; tmax were (1.43 ± 1.06 ), (3.67 ± 1.32) and (2.40 ± 0.79) h, respectively; t1 / 2 were (1.53 ± 0.44), (4.72 ± 1.27) and (3 305 ± 646) and (415 ± 103) μg · h · L -1, respectively. Conclusion The established LC-MS / MS method is accurate and sensitive and can be used for the analysis of plasma concentrations and pharmacokinetics of losartan potassium hydrochlorothiazide tablets.