建立液相色谱-质谱串联法测定大鼠微透析样品中美罗培南的浓度

LC-MS/MS Method in Determination of Meropenem Concentration of Microdialysis Samples of Rats

目的建立高效液相色谱-质谱串联法（HPLC-MS/MS）用于监测微美罗培南在透析液中实时变化的浓度,为应用微透析技术对感染靶部位美罗培南的药动/药效学研究奠定基础。方法采用COSMOSIL 5C18-PAQ（150 mm×4.6 mm,5μm）色谱柱进行分离,流动相为乙腈-0.1%甲酸水,梯度洗脱,流速1.0 ml/min,分析时间为8 min;美罗培南和内标（安替比林）均在ESI正离子模式扫描,以多反应监测（MRM）模式进行扫描,检测离子对美罗培南m/z 384.2→141.2,内标m/z 189.2→104.0。结果美罗培南在0.01～40μg/ml线性范围内线性关系良好（r=0.9979）;日内及日间精密度在9.76%以内,准确度-7.87～0.28%。结论本法灵敏度高、专属性强、精密度好、准确度高,适用于微透析样品的快速有效分析。

Objective To establish a high performance liquid chromatography-tandem mass spectrometry（ LCMS / MS） method to monitor real-time concentration changes of Meropenem during microdialysis samples of rats so as to provide the foundation for further pharmacokinetic / pharmacodynamic（ PK / PD） study of Meropenem on infected tissues with microdialysis technique. Methods Chromatographic separation was performed on a COSMOSIL 5C18-PAQ（ 150 mm × 4. 6 mm,5 μm） column by a gradient elution,the mobile phase was composed of acetonitrile and-0. 1% formic acid aqueous solution at a 1. 0 m L / min flow rate in a run time of 8 min. The quantification of Meropenem and internal standard（ Antipyrine） were determined by multiple reaction monitoring（ MRM） mode with a positive electrospray ionization（ ESI）,and the ion transitions were m / z 384. 2→141. 2 and m / z 189. 2→104. 0 for Meropenem and internal standard respectively. Results The Meropenem showed good linear correlation in a range of 0. 01-40 μg / m L（ r = 0. 9979）.The intra- and inter-day precisions [relative standard deviation（ RSD） %] were all within 9. 76%,and accuracy（ RE%） ranged from-7. 87% to 0. 28%. Conclusion The established LC-MS/MS method of Meropenem is accurate with good sensitivity,specificity and precision,which can be applied in quick and effective analysis of Meropenem concentration in microdialysis samples.