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建立了反相高效液相色谱法测定人血浆及尿中尼扎替丁浓度,并进行健康人体药动学研究。色谱柱为DiamonsilC_(18)柱,流动相为乙腈-0.05 mol/L磷酸氢二钾-三乙胺(17:83:1,v/v/v,pH 6.5),流速0.9 mL/min,紫外波长320 nm。10名健康志愿者(男女各半)单次静脉滴注尼扎替丁100 mg和多次给药(100 mg/次,3次/日,连用6天)后,测定尼扎替丁血样及尿样浓度,DAS软件计算药动学参数。血浆药物浓度在(0.0117-6)mg/mL范围内具良好线性关系(r=0.9999),尿中药物浓度在(0.029-50)μg/mL范围内呈良好线性关系(r=0.9998),定量下限为0.0117μg/mL,日内、日间精密度分别低于5.12%和8.03%(血样),6.2%和6.9%(尿样)。尼扎替丁主要药动学参数为:单剂量:C_(max)(2.7±0.6)μg/mL,t_(1/2)(1.4±0.4)h,AUC_(0-12 h)(2.45±0.33)μg·h/mL,AUC_(0-∞)(2.46±0.33)μg·h/mL,12小时尿累计排泄率为61.2%±9.46%;多剂量:C_(max)(2.9±0.8)μg/mL,t_(1/2)(1.3±0.2)h,AUC_(0-12 h)(2.56±0.52)μg·h/mL,AUC_(0-∞)(2.56±0.52)μg·h/mL,12小时尿累计排泄率为51.3%±9.42%。对单剂量、多剂量及性别的药代动力学参数进行比较,结果差异无显著性差异。多次给药体内无蓄积。该法简便、快捷、灵敏、准确,适用于尼扎替丁药代动力学研究。
An RP-HPLC method for the determination of nizatidine in human plasma and urine was established and the pharmacokinetics study of healthy human was carried out. The column was Diamonsil C 18 column with a mobile phase of acetonitrile-0.05 mol / L dipotassium phosphate-triethylamine (17: 83: 1, v / v / v, pH 6.5) Wavelength 320 nm. Ten healthy volunteers (male and female half) were given a single intravenous infusion of nizatidine 100 mg and multiple administrations (100 mg / time, 3 times daily for 6 days) Urine concentration, DAS software to calculate pharmacokinetic parameters. There was a good linearity (r = 0.9999) for plasma drug concentration in the range of (0.0117-6) mg / mL and a good linearity (r = 0.9998) in the range of (0.029-50) μg / The lower limit was 0.0117 μg / mL. The intra-day and inter-day precision were lower than 5.12% and 8.03% (blood samples), 6.2% and 6.9% (urine samples) respectively. The main pharmacokinetic parameters of nizatidine were single dose (2.7 ± 0.6) μg / mL, t 1/2 (1.4 ± 0.4) h, AUC 0-12 h (2.45 ± The cumulative urinary excretion rate at 12 hours was 61.2% ± 9.46%. The multiple dose: C max (2.9 ± 0.8) (0.56 ± 0.52) μg · h / mL, AUC_ (0-∞) (2.56 ± 0.52) μg · h / mL, 12h urine cumulative excretion rate of 51.3% ± 9.42%. Pharmacokinetic parameters of single-dose, multiple-dose and gender were compared, the results showed no significant difference. Multiple administration to the body without accumulation. The method is simple, rapid, sensitive and accurate and can be applied to study the pharmacokinetics of nizatidine.