HPLC-MS/MS法测定人血浆及尿液中奥普力农浓度  

HPLC-MS/MS determination of olprinone in human plasma and urine

作　　者：梅亚君 秦永平[2] 毛锐[2] 张梅[1] 余勤[2] 向瑾[2] 南峰[2] 梁茂植[2] 

机构地区：[1]成都中医药大学药学院中药材标准化教育部重点实验室中药资源系统研究与开发利用省部共建国家重点实验室培育基地,四川成都611137 [2]四川大学华西医院国家药物临床试验机构临床药理研究室,四川成都610041

出　　处：《中药与临床》2016年第2期52-55,80,共5页Pharmacy and Clinics of Chinese Materia Medica

摘　　要：目的:建立准确、灵敏的HPLC-MS/MS法测定人血浆及尿液中奥普力农(OLP)的浓度,以用于OLP的药代动力学研究。方法:采用API3000 LC-MS/MS液质联用系统,Phenomenex Gemini C_(18)柱(50×3.0 mm,5μm),流动相为乙腈∶2 mmol.L^(-1)甲酸铵(30∶70),流速0.2 m L.min^(-1),血浆及尿液样本在pH7.5的弱碱性环境下分别用二氯甲烷︰异丙醇(95︰5)、二氯甲烷萃取后进样,采用ESI源,正离子MRM模式检测,米力农(MIL)作内标。结果:OLP和内标MIL的保留时间分别为1.91 min和1.88 min。OLP的血浆标准曲线在(0.05~100)ng.m L^(-1)范围内线性良好(r=0.9960),定量下限为0.05 ng.m L^(-1)。日内精密度在2.0%~4.1%之间,日间精密度在4.2%~5.5%之间。方法回收率在(91.78±1.24)%^(103.12±2.64)%之间。萃取回收率在56.9%~68.1%之间。基质效应在^(-1)3.9~3.4%之间。OLP的尿液标准曲线在(1~1000)ng.m L^(-1)范围内线性良好(r=0.9954),定量下限为1 ng.m L^(-1)。日内精密度在2.0%~5.8%之间,日间精密度在2.7%~9.4%之间。方法回收率在(90.28±1.80)%^(97.82±5.68)%之间。萃取回收率在67.4%~82.3%之间;基质效应在^(-1)3.9%~^(-1)2.0%之间。稳定性各项数据均符合相关要求。结论:本法具有快速、简便、灵敏、准确等特点,适用于OLP血药浓度及尿药浓度的测定及其药代动力学研究。Objective： To develop an accurate and sensitive method for the determination of olprinone in human plasma and urine, which can be used in the pharmacokinetic study of OLP. Method： API3000 LC - MS/MS system was used. The mobile phase consisted of a mixture of acetonitrile-2mmol·L^-1 ammonium formate （30：70） was delivered at a flow rate of 0.2 mL·min^-1. Plasma samples and urine samples were respectively extracted by dichloromethane： isopropanol （95：5, v/v） and dichloromethane in the condition of pH=7.5, and then separated on a Phenomenex Gemini C18 column （50×3.0mm, 5μm）. The sample were subsequently analyzed by mass spectrometry with an ESI source and quantified by multiple reaction monitoring （MRM） mode. Milri-none was used as the internal standard. Result： The retention time of olprinone and internal standard were 1.91 min and 1.88 min, respectively. The calibration curve for plasma samples was in the range of 0.05-100 ng· mL^-1. The limit of quantification was 0.05 ng· mL^-1. Methodological recovery was （91.78±1.24）% -（103.12±2.64）%. Pretreatment recovery was 56.9%-68.1%. Matrixes effect was -13.9%-3.4%. The calibration curve for urine samples was in the range of 1-1000 ng·mL^-1. The limit of quantification was 1ng· mL^-1.Methodological recovery was （90.28±1.80） % - （97.82±5.68）%. Pretreatment recovery was 67.4%-82.3%. Matrixes effect was -12.0%- -13.9%. Data about all stability study fitted the request. Conclusion： The developed method is found to be simple, rapid, sensitive and accurate for the determination of olprinone in human plasma and urine samples and to be suitable for the pharmacokinetic study.

关 键 词：HPLC-MS/MS 奥普力农 血药浓度 尿药浓度 

分 类 号：R917[医药卫生—药物分析学]