高效液相色谱―质谱联用测定小鼠血浆中FG―4592浓度及其药动学的研究.docVIP

高效液相色谱―质谱联用测定小鼠血浆中FG―4592浓度及其药动学的研究 　　[摘要] 目的 建立LC-MS/MS法检测小鼠血浆内FG-4592的浓度，研究FG-4592在小鼠体内的药代动力学。 方法 KM小鼠腹腔注射FG-4592 5 mg/kg，不同时间点采集血浆，样品经甲醇沉淀。选用Agilent Zorbax SB-Aq-C18色谱柱（2.1 mm× 100 mm，3.5 μm），柱温25℃，流动相为甲醇-水（含5 mmol/L甲酸铵，0.1%甲酸）（90∶10），流速0.35 mL/min。采用ESI离子源，正离子模式多反应监测，离子通道分别为m/z 353.1→ m/z 278.1（FG-4592）和m/z 294.9→m/z 235.0（内标物）。 结果 测定血浆中FG-4592的线性范围为1～1000 ng/mL，日内及日间精密度均10%，准确度在90%～105%范围内，方法学考察均符合生物样品的分析要求。药代动力学参数：Cmax为（22.80±0.36）μg/mL，AUC（0-72）为（31.64±0.97）（μg?h）/mL，t1/2为8.81 h。 结论 本研究建立的FG-4592血药浓度测定方法可行，该药物在血液中吸收良好，测定结果可为药物的基础研究提供依据。 　　[关键词] FG-4592；高效液相色谱-质谱联用；药代动力学 　　[中图分类号] R969.1 [文献标识码] A [文章编号] 1673-7210（2016）03（c）-0014-05 　　[Abstract] Objective To develop a LC-MS/MS method for the quantitative analysis of FG-4592 in mice plasma and to study the pharmacokinetic profile of FG-4592 with this method. Methods KM mice were intraperitoneally administered 5 mg/kg FG-4592. The plasma samples were collected at different time points and precipitated by methanol. An Agilent Zorbax C18 （2.1 mm×100 mm， 3.5 μm） chromatographic column with the column temperature of 25℃ was used. The mobile phase consisted of methanol-water （contained 5 mmol/L ammonium formate and 0.1 % formic acid） （90∶10）. The flow rate of mobile phase was 0.35 mL/min. The analyte was monitored by positive electrospray ionization （ESI） in multiple reaction monitoring mode. The mass transition pairs was m/z 353.1→ m/z 278.1 （FG-4592） and m/z 294.9→ m/z 235.0 （internal standard） respectively. Results The calibration curve was established in concentration range of 1-1000 ng/mL. The intra-and inter-day RSDs were both less than 10%. The method recoveries were within 90%-105% and met for the requirements of biological sample analysis. The pharmacokinetic parameters were as follows： Cmax was （22.80±0.36） μg/mL， AUC（0-72） was （31.64±0.97） （μg?h）/mL， t1/2 was 8.81 h. Conclusion This method is reliable. FG-4592 is well absorbed in mice blood and the results can provide the basis for fundamental researc