Determination of biapenem in human plasma and urine by a simple HPLC method for its pharmacokinetics study  

应用HPLC法测定人血浆和尿中比阿培南浓度及药动学研究(英文)

作　　者：武晓捷[1] 郁继诚[1] 张菁[1] 曹国英[1] 施耀国[1] 张婴元[1] 

机构地区：[1]复旦大学附属华山医院抗生素研究所,上海200040

出　　处：《Journal of Chinese Pharmaceutical Sciences》2009年第2期177-182,共6页中国药学（英文版）

摘　　要：A simple high-performance liquid chromatography （HPLC） method was established and subsequently used to study the pharmacokinetics of biapenem in healthy volunteers. Chromatography separation was carried out using a C18 reverse-phase column with an isocratic mobile phase consisting of 0.05 M ammonium acetate-methanol, either for plasma （94：6, v/v, and flow rate 1.0 mL/min） or for urine samples （97.5：2.5, v/v, flow rate 1.5 mL/min）. The UV detector was set at 300 nm. The assay was linear over the range of 0.25 mg/L-50 mg/L for plasma samples and 0.50 mg/L-200 mg/L for urine samples. The intra-day and inter-day RSD values were lower than 2.8% and 4.6%, respectively, for biapenem in plasma, 2.4% and 2.5%, respectively, for biapenem in urine. Biapenem was stable at room temperature for up to 6 h in plasma and 8 h in urine when MOPS was added immediately after sample collection. An intravenous single dose of 600 mg biapenem was administered to 12 healthy male volunteers. The pharmacokinetic parameters were calculated by Winnonlin with a noncompartment model. The pharmacokinetic parameters were obtained as following： Cmax 37±6 mg/L, t1/2 1.27±0.21 h, AUC0-8h 56±8 mg/L/h, and AUC0-∞57±8 mg/L/h. The accumulated urine excretion rate in 24 h was 58%±5%. The established HPLC method was validated and suitable for the pharmacokinetic study of biapenem.建立简单高效液相方法测定人血浆及尿液中比阿培南浓度,并进行健康人体比阿培南药代动力学研究。采用C18反相色谱柱,血样0.05M乙酸铵-甲醇(94:6)洗脱,流速1.0mL/min尿样0.05M乙酸铵-甲醇(97.5:2.5)洗脱,流速1.5mL/min。紫外波长300nm。12名男性健康志愿者单次静脉滴注600mg比阿培南(60min),测定比阿培南血样及尿样浓度,Winnonlin软件非房室模型计算药动学参数。血样测定线形范围为0.25mg/L-50mg/L,尿样测定线形范围为0.50mg/L-200mg/L。日内、日间精密度分别低于2.8%和4.6%(血样),2.4%和2.5%(尿样)。血样及尿样采集后立即加入稳定剂MOPS后室温下分别在6小时和8小时内稳定。比阿培南主要药动学参数分别为:Cmax37±6mg/L,t1/21.27±0.21h,AUC0-8h56±8mg/L/h,AUC0-∞为57±8mg/L/h,24小时尿累积排出率为(58±5)%。建立的方法简单、灵敏、重现性好,可用于比阿培南药代动力学研究。

关 键 词：BIAPENEM High performance liquid chromatography PHARMACOKINETICS 

分 类 号：R96[医药卫生—药理学]