LC-MS/MS法测定人血浆中替利定和去甲替利定的质量浓度  

LC-MS/MS determination concentrations of tilidine and nortilidine in human plasma

作　　者：郝光涛[1] 白少柏[1,2] 郑专杰[1] 高洪志[1] 曲恒燕[1] 李媛媛[1] 刘泽源[1] 

机构地区：[1]军事医学科学院附属医院临床药理室,北京100071 [2]解放军第五医院药剂科,银川750004

出　　处：《药物分析杂志》2012年第10期1726-1730,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立LC-MS/MS法测定人血浆中替利定和去甲替利定的质量浓度。方法:选用Agilent-Zorbax-Eclipse-XDB-C18色谱柱,以甲醇-1 mmol·L-1醋酸铵(75∶25)为流动相,采用正离子,多反应监测方式测定样品质量浓度。用于定量分析的离子对分别为[M+H]+m/z 274.3→m/z 155.1(替利定),[M+H]+m/z 260.2→m/z 155.1(去甲替利定)和[M+H]+m/z 284.8→m/z 192.9(地西泮)。结果:血浆样品中,替利定在0.5～250 ng·mL-1范围内线性关系良好(r=0.9936),最低定量质量浓度为0.5 ng·mL-1;去甲替利定在1～500 ng·mL-1范围线性关系良好(r=0.9948),最低定量质量浓度为1 ng·mL-1。二者日内与日间RSD均小于15%,平均回收率高,且稳定性均较好。结论:本方法简便快速、灵敏准确、特异性强,适用于盐酸替利定和去甲替利定的体内药代动力学研究。Objective：To establish a high performance liquid chromatography-mass spectrometry method for the determination of tilidine and nortilidine in human plasma.Methods：The sample were separated on an Agilent-Zorbax-Eclipse-XDB-C18 column with methanol-1 mmol·L-1 ammonium acetate（75∶ 25）as the mobile phase with the multiple reaction monitoring in the positive ion mode.The transitions of ＋ m/z 274.3→m/z 155.1（tilidine）,＋m/z 260.2→m/z 155.1（nortilidine） and ＋m/z 284.8→m/z 192.9（diazepam） were used to quantify them,respectively.Results：In plasma,the calibration curve for tilidine was linear over the concentration range of 0.5-250 ng·mL-1（r=0.9936）,the minimum detectable concentration was 0.5 ng·mL-1;The calibration curve for nortilidine was linear over the concentration range of 1-500 ng·mL-1（r =0.9948）,the minimum detectable concentration was 1 ng·mL-1.The inter-and intra-day precisions（RSDs） were both less than 15%,the average recovery was high,and stabilities were good.Conclusion：The method is simple,rapid,sensitive and accurate on their pharmacokinetic study of tilidine and nortilidine in the human body.

关 键 词：高效液相色谱质谱联用法 替利定 去甲替利定 药代动力学 人血浆样品 麻醉性镇痛剂 

分 类 号：R917[医药卫生—药物分析学]