HPLC法测定人血浆中比阿培南的浓度及其药动学研究

目的:建立一种简便、快速测定人血浆中比阿培南浓度的方法,并考察其药动学。方法:血浆样品加入5-羟基吲哚乙酸20μL,经7%硫酸锌蛋白沉淀后进样测定,其中色谱柱为AgilentZorbaxBonus-RP,流动相为甲醇-0.3%醋酸水溶液(梯度洗脱),流速为1.0mL·min~(-1),紫外检测波长为300nm,进样量20μL。结果:30名健康受试者随机分为低、中、高3个剂量组单次静脉滴注,血浆中比阿培南的药动学参数分别为:t_(1/2)(1.13±0.16)、(1.06±0.10)、(1.11±0.12)h,t_(max)(1.02±0.21)、(1.10±0.31)、(1.05±0.27)h,c_(max)(9.04±4.24)、(17.64±4.55)、(35.10±4.23)μg·mL~(-1),AUC_(0～12h)(18.17±3.86)、(36.44±7.68)、(70.24±8.91)mg·h·L~(-1),AUC_(0～∞)(20.42±4.69)、(37.21±7.63)、(72.40±9.03)mg·h·L~(-1);多次给药的t_(1/2)、t_(max)、c_(max)、AUC_(0～12h)、AUC_(0～∞)分别为(1.07±1.35)h、(1.04±0.60)h、(19.61±3.68)μg·h~(-1)、(32.47±3.90)mg·h·L~(-1)、(33.36±3.80)mg·h·L~(-1)。结论:3个剂量组的药动学参数呈线性相关,各剂量组内、间无显著性个体差异,不同年龄、性别、身高、体重之间也无显著性个体差异。

Determination of Biapenem Concentration in Human Plasma by HPLC and Pharmacokinetie Study

OBJECTIVE： To establish a simple and rapid method for the determination of biapenem in human plasma and inves- tigate pharmacokinetics of it. METHODS： Plasma samples were added 5-hydroxyindoleacetic acid 20 μL and then precipitated by 7% zinc sulfate. Agilent Zorbax Bonus-RP column was used with mobile phase consisted of methanol-0.3% acetic acid solution （gradient elution） at the flow rate of 1.0 mL·min^-1. UV detection wavelength was set at 300 nm. RESULTS： 30 healthy volunteers were randomly divided into low-dose group, medium-dose group and high-dose group with single intravenous infusion. Pharmacokinetic parameters of biapenem were as follows： tile were （1.13± 0.16） h, （1.06 ± 0.10）h and （1.11 ± 0.12）h; tmax were （1.02 ±0.21）h, （1.10±0.31）h and （1.05＋0.27）h; Cmaxwere （9.04±4.24）μg·mL^-1, （17.64±4.55）μg·mL^-1and （35.10±4.23）μg·mL^-1; AUC0-12 h were （18.17 ±3.86）mg·h·L^-1, （36.44±7.68）mg·h·L^-1 and （70.24±8.91）mg·h·L^-1;AUC0-∞. were （20.42 ±4.69）mg·h· L^-1, （37.21 ±7.63）mg·h·L^-1 and （72.40±9.03） mg·h·L^-1. t1/2, tmax, Cmax, AUC0-12h and AUC0-∞ of multiple dose were （1.07±1.35） h, （1.04±0.60） h, （19.61 ±3.68）μg·h^-1, （32.47±3.90） mg·h·L^-1 and （33.36±3.80）mg·h·L^-1. CONCLUSION： Pharma- cokinetic parameters of 3 groups are in linear correlation. There is no difference in interior-group and intra-group among different dosages, as well as different age, gender, height and body weight.