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本研究成功建立了一种灵敏、快速且简单的液相色谱-质谱串联方法,用以测定裸鼠血浆中来曲唑的药物浓度,并将其应用于药物动力学研究.以阿那曲唑作为内标,血浆样本经过一步乙腈沉淀蛋白前处理后进行分析测定.采用C18反相柱(4.6 mm×250 mm,5μm),乙腈-0.1％甲酸水溶液(60∶40,v/v)为流动相组分,流速1.0 mL/min,以完成色谱分离过程.使用三重四极杆串联质谱,以电喷雾正离子模式、质谱多反应监测技术对来曲唑和阿那曲唑同时进行质谱检测.标准曲线在0.8-2000 ng/mL浓度范围内呈现良好线性(r＞0.99).该方法定量下限可达0.8 ng/mL,且日间、日内准确度、精密度均处于可接受范围.该方法成功应用于雌性BALB/c裸鼠单次口服来曲唑2 mg/kg的临床前药物动力学研究,并建立一级吸收的一室模型以描述其药物动力学行为.“,”A sensitive,rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of letrozole (LTZ) in nude mouse plasma in the current study,which was successfully applied to a pharmacokinetic study.Using anastrozole as internal standard (IS),plasma samples went through a one-step protein precipitation with acetonitrile before determination.The analyte and IS were analyzed on a reversed-phase ZORBAX-SB-C18 column (4.6 mm×250 mm,5 μtm) with an isocratic mobile phase consisting of acetonitrile and water containing 0.1％ formic acid (v/v) at a flow rate of 1.0 rnL/min.The analyte and IS were detected by a triple-quadrupole tandem mass spectrometer,and electrospray and multiple reaction monitoring (MRM) were employed to select LTZ at m/z 286.4/217.1 and IS at m/z 294.1/225.3 simultaneously in the positive ion mode.The calibration curve showed good linearity ranging from 0.8-2000.0 ng/mL (r＞0.99).The intra-day and inter-day precisions of LTZ were 4.0％-8.4％,with an accuracy of 98.6％-104.9％.Using this method,we successfully characterized the pharmacokinetics (PK) of LTZ by a one-compartment model with first-order absorption in female BALB/c nude mice.