用UHPLC-MS/MS法测定大鼠血浆中L-辛弗林的浓度  

Determination of L-synephrine in rat plasma by UHPLC-MS/MS method in pharmacokinetic study

作　　者：陈伟康 刘德鸿 郑洋滨 吴倩颖 杨毅生 CHEN Wei-kang;LIU De-hong;ZHENG Yang-bin;WU Qian-ying;YANG Yi-sheng(Jiangxi Institute for Drug Control,National Medical Products Administration Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine,Jiangxi ProvinceEngineering Research Center of Drug and Medical Device Quality,Nanchang 330029,Jiangxi Province,China;Graduate School,Jiangx University of Chinese Medicine,Nanchang 330004,Jiangxi Province,China)

机构地区：[1]江西省药品检验检测研究院,国家药品监督管理局中成药质量评价重点实验室,江西省药品与医疗器械质量工程技术研究中心,江西南昌330029 [2]江西中医药大学研究生院,江西南昌330004

出　　处：《中国临床药理学杂志》2024年第15期2256-2260,共5页The Chinese Journal of Clinical Pharmacology

基　　金：江西省重点研发计划基金资助项目(20212BBG73025);江西省药品监督管理局科研基金资助项目(2021KY44)。

摘　　要：目的建立超高效液相串联三重四极杆质谱法测定大鼠血浆中L-辛弗林的方法,并应用于药代动力学研究。方法血浆样品用乙腈涡旋沉淀蛋白,离心,氮吹干后,用流动相溶解,进样分析。色谱柱:Shiseido CAPCELL PAK CR(1∶4)色谱柱(2.0 mm×150.0 mm,5μm),柱温:25℃;流动相:乙腈-0.1%甲酸溶液含10 mmoL·L^(-1)甲酸铵(73∶27);流速:0.3 mL·min^(-1);进样量:2μL。以电喷雾离子源电离,正离子多反应监测模式进行质谱检测,并按要求开展了生物样品方法学验证。L-辛弗林以5 mg·kg^(-1)的剂量灌胃后,不同时间点采血,以考察L-辛弗林在大鼠体内的药代动力学特征。结果L-辛弗林在2~800 ng·mL^(-1)内呈现良好的线性关系,定量下限:2 ng·mL^(-1),精密度、提取回收率,基质效应、准确度、稀释效应、残留效应均符合要求。L-辛弗林的主要药代动力学参数:C_(max)为(464.83±76.68)ng·L^(-1),t_(max)为(0.67±0.26)h,t_(1/2z)为(1.89±0.48)h,AUC_(0-t)为(602.27±42.25)ng·mL^(-1)·h^(-1),AUC_(0-∞)为(612.28±41.18)ng·mL^(-1)·h^(-1)。结论建立的液质联用测定大鼠血浆中L-辛弗林浓度的方法简单、快速,可用于血浆中L-辛弗林含量的测定。Objective To establish an ultra-high performance liquid phase tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma and to study its pharmacokinetics.Methods The plasma samples were precipitated by acetonitrile vortex,centrifuged,dried by nitrogen,dissolved by mobile phase,and then analyzed.Chromatographic column:Shiseido CAPCELL PAK CR(1∶4)column(2.0 mm×150.0 mm,5μm),temperature:25℃.Mobile phase:Acetonitrile:0.1%formic acid solution(containing 10 mmoL·L^(-1)ammonium formate)(73∶27)with flow rate:0.3 mL·min^(-1)and injection volume was 2μL.The electrospray ion source ionization and positive ion multiple reaction monitoring mode were used for mass spectrometry detection,and biological sample methodology verification was carried out according to requirements.After intragastric administration with 5 mg·kg^(-1)dose of L-synephrine,blood samples were collected at different time points to investigate the pharmacokinetic characteristics of L-synephrine in rats.Results L-synephrine showed a good linear relationship in the range of 2-800 ng·mL^(-1),the lowest limit of quantification of L-synephrine was 2 ng·mL^(-1).Precision,extraction recovery,matrix effect,accuracy,dilution effect and residual effect all meet the requirements all met the requirements.The main pharmacokinetic parameters:C_(max)were(464.83±76.68)ng·L^(-1),t_(max)were(0.67±0.26)h,t_(1/2z)were(1.89±0.48)h,AUC_(0-t)were(602.26±42.25)ng·mL^(-1)·h^(-1),AUC_(0-∞)were(612.28±41.18)ng·mL^(-1)·h^(-1).Conclusion The established ultra high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma is simple and rapid,and can be used for the determination of L-synephrine in plasma.

关 键 词：L-辛弗林 超高效液相色谱-串联三重四极杆质谱法 大鼠 血浆 药代动力学 

分 类 号：R28[医药卫生—中药学]