高效液相色谱-串联质谱法测定人胎盘灌流液中奥司他韦和羧酸奥司他韦浓度  

Determination of oseltamivir and oseltamivir carboxylate in placental perfusate by HPLC-MS/MS

作　　者：姚勤[1] 黄桦[1] 郑巧玲[1] 王晶晶[1] 王晶[2] 张峻[1] 

机构地区：[1]昆明医科大学第一附属医院临床药学科,云南昆明650032 [2]昆明医科大学,云南昆明650032

出　　处：《中国新药与临床杂志》2015年第2期143-147,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金项目(81360108);云南省科技厅-昆明医科大学应用基础研究联合专项(2013FB139)

摘　　要：目的建立人胎盘灌流液中奥司他韦和羧酸奥司他韦的高效液相色谱-串联质谱（HPLC-MS/MS）测定方法。方法以甲硝唑为内标,胎盘灌流液样品经沉淀蛋白处理,色谱柱为Shim-pack XR-ODSⅡ柱（2.0 mm×75 mm,2.2μm）;0.1%甲酸-0.1%甲酸乙腈溶液为流动相,梯度洗脱,流速为0.3 m L·min-1;电喷雾电离源,正离子多离子反应监测,奥司他韦和羧酸奥司他韦定量离子对分别为m/z 313.0→166.1和m/z 285.1→197.1。结果奥司他韦和羧酸奥司他韦分别在0.41~100 ng·m L-1、4.1~1 000 ng·m L-1范围内线性关系良好,平均方法回收率89.3%~104.7%,日内及日间RSD均小于15%,稳定性考察结果良好。结论本方法可用于人胎盘灌流液中奥司他韦和羧酸奥司他韦浓度的检测。AIM To establish a HPLC- MS/MS method for determining the concentration of oseltamivir and osehamivir carboxylate in placental perfusate. METHODS Metronidazole was used as the internal standard, and samples were precipitated with acetonitrile. Analysis of osehamivir and osehamivir carboxylate was carried out on a Shim-pack XR-ODS II column （2.0 mm × 75 mm, 2.2 μm）. Gradient elution occurred using 0.1% formic acid- acetonitrile solution containing 0.1% formic acid at a flow rate of 0.3 mL·min-L Detection was performed with multiple reactions monitoring using positive electrospray ionization： m/z 313.0→166.1 for osehamivir and m/z 285.1→197.1 for osehamivir carboxylate. RESULTS Linearities were obtained from 0.41 to 100 ng·mL-2 for oseltamivir and 4.1 to 1 000 ng·mL-1 for osehamivir carboxylate. The mean recoveries were 89.3% - 104.7%. The intra-day RSD and inter-day RSD were all less than 15% and the analytes were proved to be stable. CONCLUSION The established HPLC- MS/MS method can be used for determination of osehamivir and oseltamivir carboxylate in placental perfusate.

关 键 词：奥司他韦 羧酸奥司他韦 色谱法 高压液相 光谱法 质量 电喷雾电离 胎盘灌流液 

分 类 号：R969.1[医药卫生—药理学]