液相色谱-串联质谱法测定大鼠血浆中舒巴坦的浓度及其药动学研究

发布时间：2018-08-08 14:40

【摘要】：目的:建立测定大鼠血浆中舒巴坦血药浓度的液相色谱-串联质谱(LC-MS/MS)法,探讨美罗培南、亚胺培南对舒巴坦在大鼠体内的药动学影响。方法:将18只SD大鼠随机分为舒巴坦组、美罗培南+舒巴坦组和亚胺培南+舒巴坦组,分别静脉注射给药,按规定时间点采血,血浆样品经乙酸乙酯萃取,LC-MS/MS法测定血药浓度;采用负离子模式,多重反应监测(multiple reaction monitoring,MRM),定量离子对为m/z232.3→m/z139.9(舒巴坦)和m/z423.4→m/z 207.1(头孢呋辛,内标)。经DAS 2.0.1计算药动学参数,并进行统计学比较。结果:舒巴坦在0.250~200μg·mL~(-1)范围内线性关系良好,方法学符合要求。药动学试验结果表明,合用美罗培南或亚胺培南后,舒巴坦在大鼠体内的主要药动学参数t_(max)、C_(max)、AUC、MRT、t_(1/2z)、CL_z和V_z与单用舒巴坦相比,无显著性差异。结论:和已报道的方法比较,本研究所建方法具有快速、高效,生物样品用量小的特点,适用于舒巴坦在大鼠体内药动学的研究;美罗培南、亚胺培南对舒巴坦在大鼠体内的药动学过程无明显影响,提示评价此类药物相互作用还需同时考虑药效学等方法。
[Abstract]:Aim: to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of sulbactam in rat plasma and to investigate the pharmacokinetic effects of meropenem and imipenem on sulbactam in rats. Methods: eighteen SD rats were randomly divided into three groups: sulbactam group, meropenem sulbactam group and imipenem sulbactam group. The quantitative ion pairs were m/z232.3 m/z139.9 and m/z423.4 m / z 207.1 (cefuroxime, internal standard). Pharmacokinetic parameters were calculated by DAS 2. 0. 1 and compared statistically. Results: the linear range of sulbactam was 0.250 渭 g mL ~ (-1). The results of pharmacokinetic test showed that there was no significant difference between sulbactam and sulbactam compared with sulbactam alone in the pharmacokinetics of sulbactam in rats. Conclusion: compared with the reported method, this method has the characteristics of fast, high efficiency and small amount of biological sample, which is suitable for the pharmacokinetics of sulbactam in rats. Imipenem had no obvious effect on the pharmacokinetic process of sulbactam in rats.
【作者单位】：宁夏医科大学药学院;宁夏医科大学总医院药剂科;宁夏医科大学总医院临床药理研究室;
【基金】：2010年宁夏回族自治区科技攻关计划项目宁夏医科大学校级科研项目(编号:XM2016090)
【分类号】：R965;O657.63

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