
高效液相串联质谱法测定小鼠肺组织中美罗培南的含量
Determination of meropenem in mouse lung by HPLC-MS/MS
目的:采用液相色谱-质谱串联技术(HPLC-MS/MS),建立测定小鼠肺组织中美罗培南含量的方法,为研究美罗培南在肺内分布的药动学奠定基础。方法:采用Diamonsil C18(150 mm×4.6 mm,5 μm)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-1,内标选择厄他培南。电喷雾离子化源(ESI),正负离子切换,美罗培南为正离子检测模式,内标厄他培南为负离子检测模式。多反应监测(MRM)方式进行定量分析,用于定量分析的离子对分别为美罗培南m/z 384.1→141.2,内标厄他培南m/z 474.4→265.2。结果:小鼠肺组织匀浆中美罗培南在15.625~2 000 ng·mL-1范围内线性关系良好(r=0.999 7),平均提取回收率为98.05%~102.54%,日内、日间精密度均小于15%。结论:采用本法测定小鼠肺组织中美罗培南的浓度,灵敏度高,专属性强,可用于肺组织样品中美罗培南快速有效的分析以及美罗培南在肺组织分布的药动学研究。
OBJECTIVE To develop an HPLC-MS/MS method for determining the concentration of meropenem in mouse lung and make a foundation for its pharmacokinetic study.METHODS Chromatographic separation was performed on a Diamonsil C18 column (150 mm×4.6 mm, 5 μm) and the mobile phase consisted of acetonitrile-0.1% formic acid at a flow rate of 1.0 mL·min-1, gradient elution was adopted and ertapenem was selected as the internal standard. The mass spectrometer was operated in the positive electrospray ionization mode for meropenem and the negative electrospray ionization mode for ertapenem with an electrospray ionization interface (ESI), switching between positive and negative ions. Quantification was performed to use multiple reactions monitoring (MRM) method with the ion transitions of m/z 384.1→141.2 for meropenem and m/z 474.4→265.2 for the IS (ertapenem).RESULTS The linear range of meropenem in lung was 15.625-2 000 ng·mL-1 and had a good linear relation (r=0.999 7), the average extraction recovery were 98.05%-102.54%, and RSD values were < 15%.CONCLUSION The HPLC-MS/MS method has a good performance in terms of accuracy, sensitivity and precision. It is suitable to quickly determine the concentration of meropenem in mouse lung and can make a foundation for its pharmacokinetic study.
高效液相串联质谱法 / 美罗培南 / 厄他培南 / 小鼠 / 肺组织 / 含量 {{custom_keyword}} /
HPLC-MS/MS / meropenem / ertapenem / mice / lung / concentration {{custom_keyword}} /
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河北省卫生厅科技计划基金资助项目(编号:20170106)。
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