Quantitative determination of nizatidine in human plasma and urine by high performance liquid chromatography and its pharmacokinetic study in humans  

HPLC法测定人血浆和尿中尼扎替丁浓度及药动学研究(英文)

作　　者：张玲[1] 赵艳萍[1] 乔华[2] 王婷[2] 梁莉[2] 常威[2] 李丹[2] 徐培涵[2] 

机构地区：[1]兰州大学药学院,甘肃兰州730000 [2]兰州大学第一医院药剂科药理基地,甘肃兰州730000

出　　处：《Journal of Chinese Pharmaceutical Sciences》2010年第4期279-284,共6页中国药学（英文版）

摘　　要：A validated simple and sensitive high performance liquid chromatographic（HPLC） method for the quantitative determination of nizatidine（NIZ） in human plasma and urine is reported.Reverse phase chromatographic separation of NIZ and salicylic acid（internal standard） was achieved on Diamonsil C_（18） column,using acetonitrile-0.05 mol/L K_2HPO_4-triethylamine （17：83：1,v/v/v,pH 6.5） as the mobile phase.Flow rate was 0.9 mL/min and the ultraviolet detector was set at a wavelength of 320 nm.The assay was linear over the range of 0.0117-6 mg/mL for plasma samples and 0.029-50 ug/mL for urine samples. The limit of quantification was 0.0117μg/mL.The intra- and inter-day RSD values were lower than 5.12%and 8.03%,respectively, in plasma,and 6.2%and 6.9%,respectively,in urine.A single dose of 100 mg NIZ and multiple doses of 100 mg NIZ were administered to 10 healthy volunteers through intravenous infusions.The multiple dose regimens were administered every 8 h for 6 consecutive days.The pharmacokinetic parameters were obtained as following：for single-dose,Cmax（2.7±0.6）μg/mL, t1/2（1.4±0.4） h,AUC0-12h（2.45±0.33）μg·h/mL,AUC0-∞（2.46±0.33）μg·h/mL,and the accumulated urine excretion rate in 12 h was 61.2%±9.46%;for multiple doses,Cmax（2.9±0.8）μg/mL,t1/2（l.3±0.2） h,AUC0-12h（2.56±0.52）μg·h/mL,AUC0-∞ （2.56±0.52）μg·h/mL,and the accumulated urine excretion rate in 12 h was 51.3%±9.42%.The statistical analysis of the pharmacokinetic parameters in males and females after single-dose and multiple-dose intravenous infusion of NIZ showed no differences.No drug accumulation after multiple-dose intravenous infusion of 100 mg NIZ was observed.The validated HPLC method was suitable for the pharmacokinetic study of NIZ.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。

关 键 词：NIZATIDINE RP-HPLC PHARMACOKINETICS 

分 类 号：R969.1[医药卫生—药理学]