HPLC-ESI/MS法测定大鼠血浆及脑组织中H102肽的浓度  

Determination of H102 peptide in rat plasma and brain tissues by HPLC-ESI/MS

作　　者：邵夏炎[1,2] 谭远贞[1,2,3] 刘青锋[1,2] 张弛[1,2] 查媛[1,2] 钱勇[1,2] 张奇志[1,2] 

机构地区：[1]复旦大学药学院药剂学教研室,上海201203 [2]智能化递药教育部和全军重点实验室,上海201203 [3]天津医科大学基础医学院生理学教研室,天津300192

出　　处：《中国临床药学杂志》2013年第2期67-72,共6页Chinese Journal of Clinical Pharmacy

基　　金：复旦大学药学院和智能化递药教育部重点实验室(复旦大学)开放课题(编号2011SDD-10)

摘　　要：目的建立大鼠血浆和脑组织中H102肽浓度测定的HPLC-ESI/MS法。方法血浆和脑组织样品采用甲醇沉淀蛋白后进样测定。色谱柱:Gemini C_(18)(50 mm×2.00mm,5μm),流动相:乙腈(0.1%甲酸)-水(0.1%甲酸)(14.5:85.5),流速0.4mL·min_(18),柱温40℃。采用电喷雾正离子模式离子化,选择m/z 645.3和m/z 843.2分别作为H102肽及内标安普利泰的检测离子。结果血浆及脑组织中H102肽在5~500μg·L^(-1)内线性良好(r=0.999 2,0.999 3);日内、日间精密度良好(RSD均<15%);提取回收率>85%。SD大鼠鼻腔给予H102肽溶液(2 mg·kg^(-1))后,主要药动学参数:t_(max)5 min,ρ_(max)103.13μg·L^(-1)。大鼠嗅球、大脑、小脑及海马中H102肽的AUC_(0→60min)分别为3 149.07、266.98、243.72及407.77μg·min·L^(-1)。结论本方法快速、准确、重复性好,适用于大鼠体内H102肽浓度的测定。AIM To establish a HPLC-ESI/MS method for the determination of H102 peptide in rat plasma and brain tissues. METHODS Methanol was used for protein precipitation. The separation was carded out on a Gemini Cls column （50 mmx 2.00 ram, 5 t_tm）with the mobile phase consisted d acetonitrile （0.1% formic acid）-water （0.1% formic acid） （14.5：85.5）, which was pumped at a flow rate of 0.4 mL＂ min-1. The positive ionization mode was cho- sen. The chosen ions were m/z 645.3 for H102 and m/z 843.2 for eptifibatide as internal standard, which were de- tected by electro-spray ionization （ESI）. RESULTS The liner range of H102 in rat plasma and brain tissues were 5 - 500 μg L-1（ r = 0. 999 2,0. 999 3）. The intra-day RSD and inter-day RSD for plasma and brain samples were below 15% and the extraction recovery was more than 85%. The pharmacokinetic parameters after intranasal administration with H102 were as follows： tmax was 5 min,pmax was 103.13 μg L-1. The AUC0-60min of H102 in olfactory bulb, cere- brum, cerebellum and hippoeampus were 3 149.07, 266.98, 243.72 and 407.77 μg min L- 1, respectively. CON- CLUSION A fast, accurate and good reproducible HPLC-ESI/MS method for the determination of H102 in rat plasma and brain tissues is established.

关 键 词：H102肽 HPLC-ESI MS法 血浆 脑组织 药动学 

分 类 号：R96[医药卫生—药理学]