基于HPLC-MS/MS的青风藤生物碱的药物代谢动力学研究  

HPLC-MS/MS based pharmacokinetic study of alkaloids of sinomenium acutum

作　　者：谢彤[1] 程学芳[2] XIE Tong;CHENG Xuefang(Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanfing University of Chinese Medicine, Nanjing 210023, Jiangsu, China;Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China)

机构地区：[1]南京中医药大学中医儿科学研究所/江苏省儿童呼吸疾病(中医药)重点实验室 [2]上海交通大学附属第一人民医院临床药学科,上海200080

出　　处：《中国临床药理学与治疗学》2017年第9期984-991,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金青年科学基金项目(81503138);国家自然科学基金面上项目(81303295);高等学校博士学科点专项科研基金(20133237120001);江苏省自然科学基金-青年基金项目(BK20130959)

摘　　要：目的:建立青风藤主要活性成分青风藤碱和木兰花碱在大鼠生物样品中的液质联用(LCMS/MS)分析方法,并用于研究青风藤生物碱在SD大鼠体内的药代动力学行为及特征,为青风藤的广泛研究及临床用药奠定基础。方法:(1)采用LC-MS/MS法建立并确证测定大鼠生物样品中青风藤生物碱含量的方法。(2)考察大鼠单次灌胃给予青风藤提取液(10 g生药/kg)的体内经时过程。采用LC-MS/MS测定给药后血浆中青风藤生物碱的浓度,根据测定结果计算药代动力学参数并研究其药动学规律。结果:青风藤碱和木兰花碱分别在13.8~3 530.0 ng/m L(R2=0.999 9)和5.8~2 960.0 ng/m L(R2=0.999 8)浓度范围内线性关系良好,批内与批间的相对标准偏差(RSD,relative standard deviation)均小于15%。灌胃给药后青风藤碱和木兰花碱的Cmax分别为14.88μg/m L、0.99μg/m L;Tmax分别为55.00min、57.50 min;T1/2分别为2.64 h、6.08 h;AUMC(0-t)分别为369 127.25μg·h·h·m L-1、32 143.44μg·h·h·m L-1;AUC(0-t)分别为2 482.76μg·h·m L-1、177.77μg·h·m L-1;MRT(0-t)分别为2.50 h、3.12 h。结论:本实验所建立的LC-MS/MS法具有灵敏、快速、稳定的特点;药代动力学参数表明青风藤生物碱在大鼠体内的动力学符合非房室模型,其在大鼠体内的达峰时间较短,消除过程较缓慢,血药浓度高。AIM： To establish a LC-MS/MS method for the study of pharmacokintic characteris- tics of alkaloids of sinomenium acutum in sprague dawley rat, and lay the foundation for the extensive research and clinical use of sinomenium acutum. METHODS： （ 1 ） LC-MS/MS method for the quanti- fication of alkaloids of sinomenium acutum in biological sample was developed. （2）The in vivo time course of sinomenium acutum extracts （ 10 g crude drug/kg） in rats after a single oral administration was investigated. Pharmacokinetic parameters were calculated from the concentration data determined by LC-MS/MS. RESULTS： The standard curves showed good linearity over the concentration range of sinoacutine （ 13.8-3 530.0 ng/mL, R^2 = 0.999 9 ） and magnoflorine （ 5.8-2 960.0 ng/mL, R^2 = 0.999 8 ） in rat plasma. The inter-day and intra-day precision and accuracy values of sinoacutine and magnoflorine at three levels of QC samples were less than 15%. Pharmacokinetic study in rats showed that the main parameters for sinoacutine and magno- florine were Cm=（14.88） and （0.99） μg/mL, Tmax （55.00） and （57.50） min, T1/2（2.64） and （6.08） h, AUMC（0-t） （369 127.25） and （32 143.44） μg·h·h·m L^-1, AUC（0-t） （2482.76） and （177.77）μg·h·h·m L^-1, MRT（0-t） （2.50） and （3.12） h, respectively. CONCLUSION： A sensitive, specific, and suitable LC-MS/MS method is validated for simuha- neously quantifying the concentrations of sinoacutine and magnoflorine in rat plasma. Pharmacokinetic parameters show that the alkaloids of sinomenium acutum in rats conform to the non-compartmental model, and the plasma concentration reaches its peak rapidly, the elimination process is slow with high blood concentration.

关 键 词：青风藤生物碱 LC-MS/MS 药代动力学 

分 类 号：R965.2[医药卫生—药理学]