LC-MS/MS法测定人血浆中非诺贝特酸  

LC-MS/MS determination of fenofibric acid in human plasma

作　　者：张丹[1] 刘曼[1] 王晓琳[1] 张丽娜[1] 赵红娜[1] 韩静[1] 刘会臣[1] 

机构地区：[1]航天中心医院临床药理室,北京100049

出　　处：《国际检验医学杂志》2013年第13期1688-1690,共3页International Journal of Laboratory Medicine

基　　金：航天中心医院院级课题资助项目(KY-201027)

摘　　要：目的建立快速、灵敏的测定人血浆中非诺贝特酸的LC-MS/MS方法。方法人血浆样本以甲醇沉淀蛋白后,选用Zorbax SB-C18Narrow-Bore色谱柱(150mm×2.1mm,5μm),以甲醇0.1%甲酸(80∶20,v/v)为流动相,流速为0.40mL/min;选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源(ESI),负离子方式,选择监测离子反应分别为m/z316.9→m/z230.9(非诺贝特酸)和m/z355.9→m/z312.2(内标吲哚美辛)。结果非诺贝特酸和吲哚美辛的保留时间分别为1.99min和2.08min;血浆中非诺贝特酸的线性范围为0.050 0～30.0μg/mL(r>0.99),定量下限为0.050 0μg/mL;批内、批间相对标准偏差(RSD)均小于3.0%;相对误差(RE)均不超过±9.0%的范围;平均提取回收率为(99.0±2.4)%;稳定性试验中,在储备液和各种贮存条件下的血浆中,非诺贝特酸均较稳定。结论该方法快速、灵敏、准确、专属性强、重现性好,适用于人血浆中非诺贝特酸浓度的测定,并成功应用于中国健康受试者口服非诺贝特胶囊后非诺贝特酸的药代动力学研究。Objective To develop a rapid and sensitive liquid chromatography-tandem mass spectrometric（LC-MS/MS） method for the quantitation of fenofibric acid in human plasma.Methods After protein precipitation with methanol,the analyte and internal standard（IS） were separated on a Zorbax SB-C18 Narrow-Bore analytical column with the mobile phase of methanol and 0.1% formic acid（80∶20,v/v） at a flow rate of 0.40 mL/min.Detection was performed using negative multiple reaction monitoring（MRM） mode by electrospray ionization（ESI） mass spectrometry.The MRM transitions of m/z 316.9→m/z 230.9 and m/z 355.9→m/z 312.2 were used to quantify fenofibric acid and indomethacin（IS）,respectively.Results Fenofibric acid and IS were eluted at 1.99 and 2.08 min,respectively.The calibration curve was linear over the concentration range of 0.050 0-30.0 μg/mL with the lower limit of quantitation（LLOQ） 0.050 0 μg/mL.Intra-and inter-batch relative standard deviations were both less than 3.0%,and the relative errors were within ±9.0%.The mean extract recoveries were（99.0±2.4）%.In the stability studies,fenofibric acid was found to be stable in stock solution and plasma under various storage conditions.Conclusion The established method is rapid,sensitive,accurate,selective,reliable and sufficient for the determination of fenofibric acid in human plasma,and is successfully applied to a pilot pharmacokinetic study of fenofibric acid in healthy Chinese subjects after a single oral dose.

关 键 词：非诺贝特 药代动力学 色谱法 液相 吲哚美辛 

分 类 号：R96[医药卫生—药理学]