HPLC法测定人血浆中头孢噻肟钠浓度及药动学研究

Determination of cefotaxime sodium in human plasma by HPLC and pharmacokinetic study

目的建立HPLC法灵敏、准确、快速测定头孢噻肟钠的血药浓度,考察健康受试者单次给予不同剂量(0.5、1.0、2.0 g)时体内的药动学特征,为其临床应用提供参考。方法血浆样品经乙腈和二氯甲烷处理后,采用HPLC法(4.60 mm×250 mm,4μm),以乙腈-20 mmol/L磷酸水溶液(体积比16∶84)为流动相,流速为1.0 mL/min,检测波长为234 nm,柱温为35℃,头孢拉定为内标,建立头孢噻肟钠血药浓度分析方法。采用建立的分析方法,测定静脉滴注3个不同剂量的18名受试者在给药后各时间点血浆样品中头孢噻肟钠浓度,计算和分析主要药动学参数。结果头孢噻肟钠的血浆样品线性范围为0.5000~160.0μg/mL,日内、日间精密度良好(RSD<15%),提取回收率为90.88%~92.41%。3个剂量组的药动学参数C_(max)和AUC_(0-t),随给药剂量增加而增加,C_(max)和AUC_(0-t)在剂量0.5~2.0 g范围内β的90%置信区间分别为0.79~1.21和0.87~1.04,均落在C_(max)和AUC_(0-t)的判断区间0.70~1.43和0.80~1.25范围内。结论建立的测定头孢噻肟钠血药浓度的HPLC法快速、线性良好且准确性高;药动学研究结果表明,头孢噻肟钠呈线性动力学特征,在临床上应考虑头孢噻肟钠剂量的差异对人体的影响。

Objective To establish a sensitive,accurate and rapid HPLC method for determining the plasma concentration of cefotaxime sodium(CTX),and to investigate the pharmacokinetic properties of the drug on healthy volunteers in a single dose of 0.5,1.0 and 2.0 g in order to provide support for clinical application.Methods After plasma samples were treated by acetonitrile and dichloromethane,a method for the determination of cefotaxime sodium in blood was established with(4μm,4.60 mm×250 mm)chromatographic column,20 mmol/L phosphoric acid(V/V=16∶84)as mobile phase at a flow rate 1.0 mL/min,detection wavelength 234 nm,column temperature 35℃,cefradine as internal standard.The established analytical method was used to determine the concentration of cefotaxime sodium in plasma samples of 18 subjects with 3 different doses at each time point after intravenous administration,and the main pharmacokinetic parameters were calculated and analyzed.Results The linear relationship of CTX in plasma was well within the range of 0.5000-160.0μg/mL.The within-run and between-run precisions were all less than 15%.The extraction recoveries were ranged from 90.88%-92.41%.The pharmacokinetic parameters C_(max) and AUC_(0-t) of the three dose groups increased with the increase of dosage,the 90%confidence intervals ofβfor C_(max) and AUC_(0-t) were 0.79-1.21 and 0.87-1.04 within the predetermined range of 0.70-1.43 and 0.80-1.25 in the dose range of 0.5-2.0 g.Conclusion The established HPLC method is very rapid,linear and accurate.The results of pharmacokinetic study showed that cefotaxime sodium showed linear kinetic characteristics.The effect of different doses of cefotaxime sodium on human body should be considered clinically.