摘要
目的:建立并验证基于LC-MS/MS法同时测定人血浆中达比加群酯及其代谢物浓度的方法,并将其应用于临床血药浓度监测,优化疗效,减少不良反应。方法:采用简单的一步沉淀法进行样品预处理,以达比加群-D3为内标,使用Kinetex C18柱(100?,2.1 mm×50 mm,5μm,Phenomenex);流动相为含有1 mmol·L^(-1)甲酸和1 mmol·L^(-1)醋酸铵的乙腈-水溶液,以0.3 mL·min^(-1)的流速梯度洗脱5 min。采用电喷雾离子源,正离子模式下进行多重反应监测。结果:在5~1000 ng·mL^(-1)范围内,达比加群酯及其代谢物线性关系良好(r2>0.99),定量下限为5 ng·mL^(-1)(S/N>10)。该方法选择性好,批内、批间精密度和准确度相对标准差均小于15.0%。达比加群酯及其代谢物的回收率均大于84.1%,无显著的基质效应。结论:建立了一种简单、快速、稳定、可靠的LC-MS/MS方法,用于接受达比加群酯治疗的患者血药浓度监测,可为临床调整用药提供准确的技术指导。
OBJECTIVE To establish a method for the simultaneous determination of dabigatran etexilate and its metabolites in human plasma by LC-MS/MS,and to apply it to therapeutic drug monitoring for optimizing efficacy and reducing adverse reactions.METHODS A simple one-step precipitation method was used for the plasma sample pretreatment,and dabigatran-D3 was used as the internal standard.The mobile phase consisted of 1 mmol·L^(-1) formic acid and 1 mmol·L^(-1) ammonium acetate acetonitrile in water,and the gradient elution was performed at the speed of 0.3 mL·min^(-1) for 5 min on a Kinetex C18 column(100Å,2.1 mm×50 mm,5μm,Phenomenex).The positive ion mode was selected to perform the multiple reaction monitoring in a positive ion mode using electrospray ion source.RESULTS Linear calibration curves obtained over the concentration ranges of 5^(-1)000 ng·mL^(-1) for all analytes were good(r2>0.99),and the LLQC was 5 ng·mL^(-1)(S/N>10).The inter-and intra-day precision and accuracy were lower than 15.0%.The recoveries of dabigatran etexilate and its metabolites were all above 84.1%,and there was no significant matrix effect.CONCLUSION A simple,rapid,stable and reliable LC-MS/MS method for the therapeutic concentration monitoring of patients treated with dabigatran etexilate was established,which provides valuable information for clinicians.
作者
章媛媛
赵越桃
郭宏丽
胡雅慧
陈峰
ZHANG Yuanyuan;ZHAO Yuetao;GUO Hongli;HU Yahui;CHEN Feng(Pharmaceutical Sciences Research Center,Department of Pharmacy,Children's Hospital of Nanjing Medical University,Jiangsu Nanjing 210008,China;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Jiangsu Nanjing 210009,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第19期2161-2166,共6页
Chinese Journal of Hospital Pharmacy
基金
2019年南京市卫生科技发展专项资金项目(编号:YKK19104)
江苏省卫生健康委员会特聘医学专家项目(编号:2019)。
