UPLC-MS/MS法同时测定人血浆中辛伐他汀和辛伐他汀羟基酸的浓度  

UPLC-MS/MS determination of simvastatin and simvastatin hydroxy acid in human plasma

作　　者：王巨才[1] 孟小惠[2] 杨东菁[3] 王雪芹[4] 张建革[2] 

机构地区：[1]海南省药品检验所,海口570216 [2]郑州大学药学院,郑州450001 [3]河南大学医学院,开封475001 [4]河南省食品药品检验所,郑州450003

出　　处：《药物分析杂志》2012年第9期1628-1633,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立UPLC-MS/MS法同时测定人血浆中辛伐他汀和辛伐他汀羟基酸的浓度。方法:血浆样品用甲基叔丁基醚提取,离心后取上清液氮气吹干,流动相复溶后进行UPLC-MS/MS测定。色谱柱:BEH C18(2.1 mm×50 mm,1.7μm);流动相:乙腈-0.01 mol.L-1醋酸铵(72∶28);流速:0.15 mL.min-1;柱温:40℃,进样量:8μL。电喷雾离子化(ESI),正离子模式多重反应选择离子检测(MRM),辛伐他汀、辛伐他汀羟基酸及内标洛伐他汀的检测离子对分别为:m/z 419→199,437→303,405→199。结果:血浆样品中辛伐他汀、辛伐他汀羟基酸线性范围分别为0.241～61.76 ng.mL-1(r=0.999,n=5)和0.344～88.16 ng.mL-1(r=0.997,n=5),日内、日间精密度(RSD)均小于15%,方法的平均回收率分别为100.6%和106.0%,血浆基质对血浆中的辛伐他汀和辛伐他汀羟基酸测定无干扰。结论:建立的UPLC-MS/MS法处理简单、灵敏、特异性高,定量准确,为辛伐他汀制剂的临床药代动力学研究提供了简便、准确的分析测定方法。Objective：To establish a method for simuhaneous determination of simvastatin and simvastatin hydroxy acid in human plasma by UPLC - MS/MS. Methods： The plasma sample was extracted by methyl tert - butyl ether. The resulting supernatant liquid after being centrifuged was dried by nitrogen and was analyzed by the UPLC - MS/ MS method after it was diluted quantitatively by mobile phase under following chromatographic conditions：BEH C^s （2. 1 mmx 50 mm, 1.7 μm） , the mobile phase consisting of acetonitrile - O. O1 ml.L -1 ammonium acetate （ 72 ： 28 ） , with flow rate of 0. 15 mL·min -1, column temperature at 40 ℃, and sample volume of 8 μL. The re- sults of positive ion MRM detection of simvastatin and simvastatin hydroxy acidwere m/z 419-→199,and m/z 437→303, respectively, using lovastatin （m/z 405--199）as the internal standard. Results： A good linearity of simvastatin was shown in the range of 0. 241 - 61.76 ng·mL-1 （ r = 0. 999, n = 5 ） ; of simvastatin hydroxy acid, 0. 344 - 88.16ng·mL-1（r =0. 997, n =5）. Simvastatin＇s and simvastatin hydroxy acid＇s intra- day RSD and inter- day RSD were less than 15%. The average recoveries were 100. 6% and 106. 0% ,respectively. The plasma matrix had no effect on the quantification of simvastatin and simvastatin hydroxy acid. Conclusions： A rapid, sensitive and ac- curate UPLC - MS/MS method was developed and it was proved to be effective for the determination of simvastatin and simvastatin hydroxv acid in human plasma.

关 键 词：辛伐他汀 辛伐他汀羟基酸 抑制剂 药物前体 内酯药物 活性代谢物 血药浓度 药代动力学 超高效液相色谱-质谱联用法 

分 类 号：R917[医药卫生—药物分析学]