高效液相色谱-串联质谱法测定健康女性使用塞克硝唑栓后体内塞克硝唑的浓度及其药动学研究

发布时间：2018-09-08 13:45

【摘要】：目的:建立快速灵敏高效液相色谱-串联质谱(HPLC-MS/MS)法测定健康女性使用塞克硝唑栓后体内塞克硝唑栓的浓度,并研究其在体内的药代动力学特征。方法:色谱柱Welch Ultimate C_(18)(2.1 mm×50 mm,5μm);流动相:乙腈-0.1%乙酸+5 mmol·L~(-1)乙酸铵水溶液(12∶88,V/V);流速:0.5 mL·min~(-1),进样量5μL。采用ESI+源,多重反应监测(MRM)模式,对离子反应m/z186.3→128.3(塞克硝唑)和m/z192.4→128.3(Secnidazole-d6)进行监测。20名健康女性受试者,单次与多次给药试验各10名,分别给予塞克硝唑栓。根据检测的血浆中塞克硝唑浓度,用DAS 3.2.7进行数据处理以及SPSS 19.0对结果进行统计分析。结果:塞克硝唑在0.05~8.0mg·L~(-1)范围内线性良好(r0.99),定量下限0.05 mg·L~(-1),批间、批内RSD皆小于15%。健康女性血浆中塞克硝唑栓单剂量C_(max)(3.00±0.96)mg·L~(-1),t_(max)(8.90±2.68)h,t_(1/2)(18.07±2.96)h,AUC_(0-96)(97.78±35.81)mg·L~(-1)·h~(-1),AUC_(0-∞)(101.11±36.96)mg·L~(-1)·h~(-1);多剂量C_(max,ss)(6.01±2.01)mg·L~(-1),t_(max)(7.20±2.86)h,t_(1/2)(21.87±7.60)h,AUC_(ss)(107.15±33.62)mg·L~(-1)·h~(-1),AUC_(0-96)(202.11±82.07)mg·L~(-1)·h~(-1),AUC_(0-∞)(217.47±103.50)mg·L~(-1)·h~(-1)。结论:该方法灵敏、准确、可靠,专属性强,适用于塞克硝唑栓在人体内的药代动力学研究。
[Abstract]:Objective: to establish a rapid and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of Sai Ke nitrazole suppository in healthy women after treatment with Sai Ke niazole suppository and to study its pharmacokinetic characteristics. Methods: Welch Ultimate C18 (2.1 mm 脳 50 mm,5 渭 m);) mobile phase: acetonitrile-0.1% acetic acid 5 mmol L ~ (-1) ammonium acetate aqueous solution (12: 8 V / V), flow rate: 0.5 mL min~ (-1), sample volume 5 渭 L. By using ESI source and multiple reaction monitoring (MRM) model, 20 healthy female subjects were monitored for ion-reactive m/z186.3 128.3 (Sai Ke nitrazole) and m/z192.4 128.3 (Secnidazole-d6). 10 healthy women were treated with Sai Ke niazol suppository respectively. According to the concentration of Sai Ke in plasma, the data were processed with DAS 3.2.7 and the results were statistically analyzed by SPSS 19.0. Results: Sai Ke nidazole had a good linearity in the range of 0.05~8.0mg L ~ (-1) (r ~ (0.99), the lower limit of quantification was 0.05 mg L ~ (-1), and the RSD of interassay and intra-assay was less than 15 ~ (-1). 鍋ュ悍濂虫，

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