LC-MS/MS同时测定比格犬血浆中非洛地平和美托洛尔  

Simultaneous Determination of Felodipine and Metoprolol in Beagle Dog Plasma Using On-Line Solid Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry

作　　者：陈美玲[1] 张礼金[2] 周杰兆 程晓慧[1,4] 刘燕[1] 李志平[1] 李迎[1] 梅兴国[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]云南中医学院药学院,云南昆明650500 [3]武汉工程大学化工与制药学院,湖北武汉430070 [4]湖北科技学院药学院,湖北咸宁437000

出　　处：《解放军药学学报》2016年第3期202-205,210,共5页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金;No.81102498

摘　　要：目的建立同时测定比格犬血浆中非洛地平和美托洛尔的LC-MS/MS法。方法分析柱为Accucore a Q色谱柱（50 mm×2.1 mm,2.6μm）。质谱采用电喷雾离子源（ESI）,采用多反应监测（MRM）,检测离子为正离子,分别选择m/z 384/338.1、268/74.2和436.2/207.1作为非洛地平、美托洛尔和内标（缬沙坦）的检测离子对。结果非洛地平、美托洛尔的线性范围分别为0.2～100、2～800 ng·ml-1,相关系数分别为0.9977和0.9959,批内精密度分别在1.2%～2.4%和0.7%～0.8%,基质效应分别在100.4%～103.9%和98.2%～100.9%,回收率分别在97.6%～98.5%和92.0%～101.7%。结论本法操作简单、方法准确可靠、检测灵敏度高,可以用于复方非洛地平美托洛尔缓释片比格犬体内的药代动力学研究。Objective To develop an LC-MS/MS method for simultaneous determination of felodipine and meto- prolol in beagle dog plasma. Methods The chromatographic separation was achieved on an Accucore aQ （50 mm × 2. 1 mm,2.6 μm） analytical column. The multiple reaction monitoring mode of the positive ion was adopted during MS detection,and precursors to the product ion transitions of m/z 384/338.1,268/74.2 and 436.2/207.1 were used to meas- ure felodipine, metoprolol and the internal standard （valsartan）. Results There was a linear relationship over the concen- tration of 0.2 -100 ng .ml-1 and 2 -800 ng .ml-1 with a correlation coefficient （ r ） of 0. 9977 and 0. 9959,respectively. The average intra-day precision value （RSD） was 1.2% -2.4% for felodipine and 0. 7% -0.8% for metoprolol. The matrix effect value was 100.4% - 103.9% for felodipine and 98.2% - 100.9% for metoprolol. The average recovery val- ue was 97.6% -98.5% for felodipine and 92.0% -101.7% for metoprolol. Conclusion This analytic method is simple, accurateand sensitive,so it can be used for pharmacokinetic research of felodipine （5 mg） and metoprolol （50 mg） extendedrelease tablets in beagle dogs.

关 键 词：高效液相色谱 质谱法 非洛地平 美托洛尔 比格犬 血浆 

分 类 号：R917[医药卫生—药物分析学]