摘要
目的:建立LC-MS/MS法测定人血浆中辛伐他汀和辛伐他汀酸。方法:血浆样本以乙醚-二氯甲烷(3∶2)液液萃取后,选用Inertsil ODS-SP色谱柱(75 mm×2.1 mm,3μm),以乙腈-1 mmol.L-1乙酸铵(pH 4.50)(75∶25)为流动相,流速为0.25 mL.min-1;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,同一分析周期内正负离子扫描切换。辛伐他汀及其内标洛伐他汀采用正离子检测,选择监测离子反应分别为m/z 436.4→m/z199.3(辛伐他汀)和m/z 405.4→m/z 199.3(洛伐他汀);辛伐他汀酸及其内标洛伐他汀酸采用负离子检测,选择监测离子反应分别为m/z 435.3→m/z 115.0(辛伐他汀酸)和m/z 421.2→m/z 101.0(洛伐他汀酸)。结果:辛伐他汀、洛伐他汀、辛伐他汀酸、洛伐他汀酸的保留时间分别为2.78,2.33,1.47,1.38 min;血浆中辛伐他汀和辛伐他汀酸的线性范围均为0.100~15.0μg.L-1(r>0.9950),定量下限均为0.100μg.L-1;日内、日间精密度(RSD)均小于15%;准确度(RE)均在±15%的范围以内;辛伐他汀和辛伐他汀酸的平均提取回收率分别为(77.9±2.6)%和(86.1±6.1)%;平均基质效应因子分别为(95.3±4.5)%和(73.2±3.5)%;稳定性试验中,在各种贮存条件下血浆中辛伐他汀和辛伐他汀酸均较稳定。结论:该方法专属性强,灵敏度高,重现性好,适用于辛伐他汀临床药代动力学研究。
Objective:To develop an LC-MS/MS method for determination of simvastatin and simvastatin acid in human plasma.Methods:After extraction with diethylether-dichlormethane(3∶ 2),the analytes and internal standards were separated on an Inertsil ODS-SP analytical column(75 mm×2.1 nm,3 μm) with the mobile phase of acetonitrile and 1 mmol·L1 ammonium acetate(pH 4.50)(75∶ 25) at a flow rate of 0.25 mL·min1.Detection was carried out by electrospray ionization mass spectrometry in multiple reaction monitoring(MRM) mode.The positive and negative ion switching technology was performed in the same analysis run.The positive ion scan mode was used to detect simvastatin and lovastatin(I.S.) while the negative ion scan mode was used to detect simvastatin acid and lovastatin acid(I.S.).The MRM transitions of m/z 436.4→m/z 199.3 and m/z 405.4→m/z 199.3 were used to quantify simvastatin and lovastatin while m/z 435.3→m/z 115.0 and m/z 421.2→m/z 101.0 were used to quantify simvastatin acid and lovastatin acid.Results:Simvastatin,lovastatin,simvastatin acid and lovastatin acid were eluted at 2.78 min,2.33 min,1.47 min and 1.38 min,respectively.The calibration curves were linear over the concentration range of 0.100-15.0 μg·L-1 with the lower limit of quantitation 0.100 μg·L-1.Both inter-and intra-day relative standard deviations were less than 15%,and the relative errors were within 15%.The extraction recoveries of simvastatin and simvastatin acid were(77.9±2.6)% and(86.1±6.1)%;the matrix effect factors were(95.3±4.5)% and(73.2±3.5)%,respectively.In the stability studies,simvastatin and simvastatin acid in plasma were found to be stable under various storage conditions.Conclusion:The LC-MS/MS method is selective,sensitive,reliable and suitable for the clinical pharmacokinetic study of simvastatin.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2012年第8期1339-1345,共7页
Chinese Journal of Pharmaceutical Analysis