摘要
目的:建立一种快速、准确、灵敏度高、专属性强的高效液相色谱-串联质谱法(LC-MS/MS)测定人血浆中阿托伐他汀的浓度。方法:以氟伐他汀为内标,血浆样本经乙腈(含0.05%甲酸)沉淀蛋白后进行LC-MS/MS分析测定。色谱条件:采用MSCB-2C (3.0 mm×50 mm,3.3μm) C_(18)为色谱柱,以0.05%甲酸-10%甲醇-水为流动相A,0.05%甲酸-40%甲醇-60%乙腈为流动相B,等度洗脱(流动相A∶B=36∶64,V/V),流速为0.5 mL·min^(-1),柱温为45℃,进样量为5μL;质谱条件:采用电喷雾(ESI)正离子模式,多反应监测(MRM)方式进行检测,阿托伐他汀及氟伐他汀(内标)的离子对分别为559.45→250.20,412.25→224.15。结果:阿托伐他汀在1.0~100 ng·mL^(-1)范围内线性关系良好(R^(2)≥0.999 5),定量下限为1.0 ng·mL^(-1);低、中、高3水平血浆质控浓度批间及批内精密度在±10%以内,准确度在92.9%~101.3%之间,提取回收率在96.8%~102.3%范围内。短期及长期稳定性良好,无显著基质效应的影响。结论:该方法血浆样本前处理操作简单,LC-MS/MS定量分析方法快速、灵敏、准确,可用于临床阿托伐他汀的治疗药物监测。
OBJECTIVE To establish a rapid,accurate,sensitive,and specific high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for determining atorvastatin in human plasma.METHODS Fluvastatin was used as the internal standard(IS),and the plasma samples were extracted via protein precipitation using acetonitrile containing 0.05% formic acid before the analysis by LC-MS/MS.Chromatographic conditions were as follows:an MSCB-2C(3.0 mm×50 mm,3.3 μm) C_(18) column was employed with a mobile phase of 10% methanol-water(containing 0.05% formic acid)(mobile phase A)-40% methanol-60% acetonitrile(containing 0.05% formic acid)(mobile phase B)(A∶B=36∶64,V/V),the column was maintained at a constant temperature(45 ℃),injection volume was 5 μL,mobile phase was at a flow rate of 0.5 mL·min^(-1).MS conditions were as follows:an electrospray positive ion mode was used with multiple reaction monitoring detection,and ion pairs were m/z 559.45→250.20 for atorvastatin and 412.25→224.15 for IS.RESULTS The range of the calibration curve was(1.0-100) ng·mL^(-1) with a good correlation coefficient of R^(2)≥0.999 5.The lowest quantification limit was 1.0 ng·mL^(-1).The inter-and intra-day precision(RSD%) of three-level quality control plasma samples was 10%,the accuracy(RE%) was between 92.9% and 101.3%,and the extraction recovery was between 96.8% and 102.3%.Furthermore,the atorvastatin plasma samples were stable in both short and long term,and not affected by the matrix effect.CONCLUSION A simple pretreatment is used for atorvastatin plasma samples,and the method is rapid,sensitive,and accurate,and has been successfully applied to the therapeutic drug monitoring of atorvastatin.
作者
李涛
蔡华山
肖丹
程静萍
LI Tao;CAI Huashan;XIAO Dan;CHENG Jingping(Department of Pharmacy,West China Hospital,Sichuan University,Sichuan Chengdu 610000,China;Health Management Center,General Practice Medical Center,West China Hospital,Sichuan University,Sichuan Chengdu 610000,China;Department of Pharmacy,Jiuxing Nephrotic Hospital of Chengdu Wuhou District,Sichuan Chengdu 610000,China;Department of Pharmacy,Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region(Hospital.C.T.),Sichuan Chengdu 610000,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第13期1479-1483,共5页
Chinese Journal of Hospital Pharmacy
