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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-4mM甲酸铵溶液(用甲酸调节pH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/mL (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.“,”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 μrm) 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 0.5-400 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 pharmacokinetic study of deflazacort on female nude mice administered with a single oral dose of 4 mg/kg deflazacort,and its pharmacokinetics was characterized by a two-compartment model with first-order absorption.