LC-MS/MS法测定小鼠血浆及组织中伊曲康唑浓度

LC-MS/MS determination of itraconazole in mice plasma and its tissue

目的:建立LC-MS/MS法测定小鼠血浆及组织中伊曲康唑的浓度。方法:以尼莫地平为内标,采用乙腈-水-甲酸(80∶20∶0.2)为流动相,以Waters XTerraMS-C18色谱柱(2.1mm×150mm,3.5μm)为分析柱,流速为0.2mL·min-1,采用电喷雾电离(ESI),以多反应离子监测(MRM)方式进行正离子检测。用于定量分析的离子反应分别为m/z705.3→392.1(伊曲康唑)和m/z419.3→343.3(内标,尼莫地平)。结果:测定血浆及组织中伊曲康唑的线性范围为10.0～1600.0μg·L-1,定量下限为10.0μg·L-1。日内、日间精密度(RSD)小于9.7%,方法回收率为99.0%～109.8%。结论:本方法灵敏度高、专属性强、操作简便,适用于伊曲康唑脂质体在小鼠体内组织分布研究。

Objective：To establish an LC-MS/MS method for the determination of itraconazole in plasma and tissue of mice.Methods：A Waters XTerraMS-C18 column（2.1 mm×150 mm,3.5 μm）was adopted with the mobile phase consisted of acetonitrile-water-formic acid（80∶20∶0.2,v/v/v）at a flow rate of 0.20 mL·min-1.Nimodipine was used as the internal standard.Waters Micromass Quattro API tandem mass spectrometer equipped with electrospray ionization source（ESI）was used as detector operated in the positive ion mode.Multiple reaction monitoring（MRM）with the precursor to product ion combinations of m/z 705.3→392.1 and m/z 419.3→343.3 were performed to quantify itraconazole and the internal standard（nimodipine）,respectively.Results：The linear calibration curves were obtained in the concentration range of 10.0-1600.0 μg · L-1.The lowest limit of quantification was 10.0 μg·L-1 .The inter-and intra-day precision（RSD）was less than 9.7%.The method recoveries were within 99.0%~109.8%.Conclusion： The method was proved to be sensitive,rapid,convenient and suitable for tissue distribution of itraconazole liposomes in mice.