UPLC-MS/MS法测定比格犬血浆中阿司匹林、水杨酸和单硝酸异山梨酯的浓度  

UPLC-MS/MS determination of acetylsalicylic acid,salicylic acid and isosorbide-5-mononitrate in dog plasma

作　　者：向志雄[1] 刘海燕[1] 孙星[1] 徐佳珺 刘文丽[1] 

机构地区：[1]上海医药集团股份有限公司中央研究院,上海201203

出　　处：《药物分析杂志》2012年第9期1638-1643,1647,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立灵敏的超高效液相色谱-质谱联用法测定比格犬血浆中的阿司匹林、水杨酸和单硝酸异山梨酯的浓度。方法:选用Waters BEH C18(100 mm×2.1 mm,1.7μm)色谱柱,分别以0.5%甲酸/5 mmol.L-1醋酸铵-乙腈和2 mmol.L-1醋酸铵-乙腈为流动相,采用梯度洗脱进行分离,样品采用乙酸乙酯提取后进样,通过电喷雾电离源,以多重反应监测(MRM)方式进行负离子检测,用于定量分析的离子对分别为m/z 178.9→136.9(阿司匹林)、m/z 136.9→64.9(水杨酸)和m/z 293.7→250.0(内标,双氯酚酸钠)测定阿司匹林和水杨酸;m/z 249.6→58.9(单硝酸异山梨酯)和m/z 293.7→250.0(内标,双氯酚酸钠)测定单硝酸异山梨酯。结果:阿司匹林、水杨酸和单硝酸异山梨酯的线性范围分别为2.0～2000.0,20.0～16000.0,9.6～9557.0 ng.mL-1;定量下限分别可达2.0,20.0,9.6 ng.mL-1;日内、日间精密度(RSD)均小于15%。结论:本方法灵敏度较高,血浆用量少,适用于比格犬血浆样品中阿司匹林、水杨酸和单硝酸异山梨酯的测定和药物动力学研究。Objective ：To develop an UPLC - MS/MS method metabolite （ salicylic acid, SA） , isosorbide - 5 - mononitrate （ 5 for determination of acetylsalicylic acid （ASA） and its - ISMN） in dog plasma. Methods ： The dog plasma was extracted by ethyl acetate ,and separated on a BEH C18 （100 mm × 2. 1 mm, 1.7 μm）column by gradient elu- tion using acetonitrile - 0. 5 % formic acid - 5 mmol .L- 1 ammonium acetate and acetonitrile - 2 mmol. L-1 am- monium acetate as mobile phases respectively. A tandem mass spectrometer equipped with electrospray ionization source was adopted as the detector. Multiple reaction monitoring（MRM） transitions of m/z 178.9---~136.9, m/z 136.9--~64.9, m/z 249.6---~58.9 and m/z 293.7---~250. 0 were measured in negative mode for ASA, SA ,5 - ISMN and internal standard,respectively. Results：The linear concentration ranges of the calibration curve for ASA, SA, 5 - ISMN were 2.0 -2000. 0 ng . mL-1 ,20.0 - 16000.0 ng.mL-1 and 9.6 -9557.0 ng . mL-1 ,respectively;the lower limits of quantification was 2.0,20.0,9.6 ng . mL- 1, respectively ; the intra - day and inter - day relative standard deviations over the entire concentration range were less than 15%. Conclusion： The method is sensitive and suitable for pharmacokinetic study of ASA, SA and 5 - ISMN in dog subjects.

关 键 词：超高效液相色谱-质谱联用法 阿司匹林 水杨酸 单硝酸异山梨酯 比格犬血浆样品检测 血药浓度 

分 类 号：R917[医药卫生—药物分析学]