应用LC-MS/MS法研究茶多酚在大鼠体内的多组分药动学  

Application of LC-MS/MS method in pharmacokinetic study of multi-components from tea polyphenols in rats

作　　者：李秋莎[1] 王长远[1] 韩国柱[1] 邹玲莉[1] 吕莉[1] 李楠[2] 

机构地区：[1]大连医科大学药学院,大连116044 [2]大连理工大学分析化学教研室,大连116027

出　　处：《中国新药杂志》2011年第9期817-824,共8页Chinese Journal of New Drugs

基　　金：大连市政府科技基金(2002E4NS044)

摘　　要：目的：建立一种LC-MS/MS法同时测定大鼠血浆中茶多酚的4种儿茶素类抗氧化活性成分,进而研究其多组分药动学。方法：选用Hypersil ODS C18柱,甲醇-水（30∶70）为流动相,等度洗脱;ESI离子源,多反应离子监测,负离子扫描。血浆样品经EtOAc液-液萃取;采用峰面积内标法定量。结果：各待测物和内标不受基质干扰,LLOQ达10或5 ng.mL-1;血浆QC样品批内和批间精密度（RSD）〈12%,准确度在97%~106%;萃取回收率〉72%,基质效应为88%~106%。大鼠iv茶多酚50和100 mg.kg-1后4种儿茶素类的血浆药动学均符合三室模型,酯型儿茶素类的消除半衰期t1/2γ较长,但非酯型t1/2γ较短;4种活性成分的Vd均大于总体水体积。po茶多酚后药时曲线呈双峰或多峰现象,但胆瘘大鼠无此现象;po生物利用度〈15%。结论：本实验建立的LC-MS/MS法高度灵敏、特异且精密,茶多酚自深室的消除较慢,分布广泛;po生物利用度较低,药时曲线双峰现象与EHC有关。酯型儿茶素类与非酯型儿茶素类药动学存在明显差异。Objective：To develop a LC-MS/MS method to simultaneously determine 4 main active catechins from tea polyphenols（TP） in rat plasma,and to study pharmacokinetics（PK） of multi-components from TP in rats.Methods：The 4 components were separated on a Hypersil C18 column using MeOH-H2O（30∶70） as an isocratic mobile phase.An ESI ion source was used and operated in the negative ion mode with MRM.Plasma samples were extracted with EtOAc.Results：In this method,detection of 4 components and IS was not interfered by the matrix.LLOQ was 10 or 5 ng·mL-1;precision（RSD） was 12%;accuracy was 97%~106%;RE was 72%;ME was 88%~106%.After iv injection of TP 50 and 100 mg·kg-1,a tri-exponential decay of plasma concentration of 4 catechins was observed;t1/2γ of EGCG and ECG were longer than those of EGC and EC.The Vd values of 4 catechins were larger than total body water volume.After oral administration of TP,the double or multi-peak C-T curves were evident in normal rats,but not in rats with bile fistulization.The oral bioavailability of TP was 15%.Conclusion：The established LC-MS/MS method is highly sensitive,specific,precise and accurate.The PK of TP complies with 3-compartment model with slow elimination from deep compartment and wide distribution.Oral bioavailability is low.The double peak C-T phenomenon is related to EHC.PK behaviors of ester-type catechins differ obviously from those of non-ester-type catechins.

关 键 词：LC-MS/MS 茶多酚 生物利用度 药动学 

分 类 号：R945.1[医药卫生—微生物与生化药学]