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目的建立气相法(质谱检测器)测定实验大鼠血浆中甲硝唑的浓度,研究灌胃给药和腹腔注射给药后体内药代动力学特点,为临床应用提供参考依据。方法大鼠分别灌胃给予甲硝唑100mg·kg-1和腹腔注射给药5mg·kg-1后,眼底静脉丛取血,分离血浆,经甲基叔丁基醚萃取后进行GC-SIM-MS分析,测定血浆甲硝唑浓度,经DAS药动学软件处理数据。结果甲硝唑在5.0～1000ng·mL-1内线性关系良好,Y=0.0377X+0.352,r=0.9997,最小定量限为5.0ng·mL-1,方法回收率为96.8%～107.6%。大鼠灌胃和腹腔注射甲硝唑后的药-时曲线均符合一房室模型。结论本实验建立的GC-SIM-MS测定法,专属、准确、灵敏,适用于甲硝唑的药动学研究。
Objective To establish a method for the determination of metronidazole in plasma of rats by gas chromatography (MS), study the pharmacokinetics of gavage in rats after intragastric administration and intraperitoneal injection, and provide reference for clinical application. Methods Metronidazole 100 mg · kg-1 and intraperitoneal injection of 5 mg · kg-1 were administered intragastrically to take blood from the venous plexus. Plasma was separated and extracted with methyl tert-butyl ether MS analysis, determination of plasma metronidazole concentration, the DAS pharmacokinetic software processing data. Results Metronidazole showed a good linearity in the range of 5.0-1000 ng · mL-1, with a Y = 0.0377X + 0.352, r = 0.9997 and a minimum limit of quantification of 5.0 ng · mL-1. The recoveries of metronidazole ranged from 96.8% to 107.6%. The drug-time curves of rats after intragastric and intraperitoneal injection of metronidazole are in line with a one-compartment model. Conclusion The established GC-SIM-MS assay is specific, accurate and sensitive and is suitable for the study of metronidazole pharmacokinetics.