A highly sensitive LC-MS/MS method for the determination of 21-hydroxy deflazacort in nude mice plasma and its application to a pharmacokinetic study  

液相色谱-串联质谱测定裸鼠血浆中21-羟基地夫可特的高灵敏方法及其在药物动力学研究中的应用(英文)

作　　者：姚庆宇[1] 李健[1] 姚烨[1] 陈镕[1] 陈文君[1] 苏红[1] 杨亮[1] 薛钧升 卢炜[2,1] 周田彦[2,1] 

机构地区：[1]北京大学医学部药学院药剂学系,北京100191 [2]北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2017年第6期404-412,共9页中国药学（英文版）

基　　金：National Natural Science Foundation of China(NSFC,Grant No.81673500)

摘　　要：In the current study, we established and validated a simple and sensitive liquid chromatography-tandem mass spectrometric method for the determination of 21-hydroxy deflazacort in nude mice plasma, and such a method was applied to a pharmacokinetic study. Using betamethasone as the internal standard, the plasma samples were pre-treated by precipitation with acetonitrile and then analyzed on a reversed-phase C18 column （50 mm×2 mm, 5 μm） with a mobile phase consisting of acetonitrile and 4.0 mM ammonium formate （pH was adjusted to 3.5 with formic acid （40：60, v/v））. The analyte was detected by a triple quadrupole tandem mass spectrometer using electrospray, and multiple reaction monitoring was employed to select 21-hydroxy deflazacort at m/z 400.2/124.0 and betamethasone at m/z 393.3/147.0 in the positive ion mode. The calibration curves were linear （r〉0.99） over the range of 0.5~,00 ng/mL. The intra- and inter-day precisions and accuracies were 4.5%-10.1% and -1.7%-10.7% respectively. This method was successfully applied to a preclinical administered with a single oral dose of 4 mg/kg deflazacort, and its pharmacokinetic study of deflazacort on female nude mice pharmacokinetics was characterized by a two-compartment model with first-order absorption.本研究建立并验证了一种简单、灵敏的液质联用方法用于测定裸鼠血浆中21-羟基地夫可特的浓度,并将此方法应用于药物动力学研究。选择倍他米松作为内标,血浆样品采用乙腈进行蛋白沉淀处理之后,用乙腈–4 mM甲酸铵溶液(用甲酸调节p H值至3.5,40:60,v/v)作为流动相,在C18反相色谱柱(50 mm×2 mm,5μm)中进行分离。质谱检测使用三重四级杆串联质谱,电喷雾正离子模式、质谱多反应监测技术对待测物21-羟基地夫可特和内标物倍他米松分别在质核比为400.2/124.0和393.3/147.0处进行检测。标准曲线的线性范围为0.5至400 ng/m L(r>0.99),日内日间的精密度为4.5%~10.1%,准确度为–1.7%~10.7%。运用该方法成功地进行了雌性Balb/c裸鼠口服单次给药4 mg/kg地夫可特的临床前药物动力学研究,采用一级吸收二室模型描述其药物动力学行为。

关 键 词：DEFLAZACORT 21-Hydorxy deflazacort LC-MS/MS Nude mice PHARMACOKINETICS 

分 类 号：R965[医药卫生—药理学]