LC_MSMS测定伊曲康唑脂质体小鼠血浆中浓度.docVIP

LC-MS/MS测定伊曲康唑脂质体小鼠血浆中浓度 魏华1，刘艳1，董迪1，宋笑丹2，吴琳华1* (1. 哈尔滨医科大学附属第二医院药学部；黑龙江省高校重点实验室，哈尔滨 150086；2. 哈尔滨医科大学附属第一医院药学部，哈尔滨 150001) 摘要:目的　建立LC-MS/MS测定小鼠血浆中伊曲康唑浓度的方法。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Cl8色谱柱(XTerra?MS-C18，2.1×150 mm, 3.5 μm)为分析柱，流速为0.2 mL . min-1，通过正离子电离(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/z 705.3→m/z 392.1(伊曲康唑)和m/z 419.3→m/z 3(内标，尼莫地平)。结果　测定血浆中伊曲康唑的线性范围为10-10 ng . mL-1，定量下限为10.00 ng . mL-1。日内、日间精密度(RSD)小于10%，回收率大于%。结论 本法专属性强、灵敏度高、操作简便、适用于伊曲康唑脂质体在小鼠体内药代动力学研究。　 关键词:伊曲康唑；液相色谱-质谱联用法；脂质体；血浆药物浓度 LC-MS/MS Determination of Itraconazole Liposome in Mice Plasma WEI Hua1, LIU Yan, DONG Di1, SONG Xiao-dan2, WU Lin-hua1* (1. Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Key Laboratory of College in Heilongjiang Province, Harbin 150086, China; 2. Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China) ABSTRACT: OBJECTIVE To establish a LC-MS/MS method for the determination of itraconazole in mice plasma. METHODS Nimodipine was used as the internal standard. Itraconazole was separated using a Cl8 column（Waters XTerra?MS-C18，2.1×150 mm, 3.5 μm).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. 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→m/z 392.1 and m/z 419.3→m/z 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 10-1280 ng·mL-1 .The lowest limit of quantification was 10.0 ng·mL-1 . The inter-and intra-day precision（RSD）was less than 10% .The average recoveries were above 90% . CONCLUSION The method was proved to be sensitive, rapid, convenient and suitable for pharmacoki