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本研究建立了一种快速、灵敏的定量方法,检测beagle犬口服达比加群酯纳米混悬剂后血浆中达比加群的浓度.采用液-质谱/质谱方法,使用反相C1s柱,以甲醇-甲酸缓冲液为流动相进行梯度洗脱,以盐酸舍曲林为内标,流速为0.4 mL/min.达比加群[M+H]+H]+m/z 472.17→289.07,舍曲林[M+H]+m/z 305.98→275.00,正离子模式,质谱多反应监测扫描方式检测样品中达比加群的浓度.研究结果表明,达比加群在1.0-500 ng/mL浓度范围内具有良好线性(r=0.9995),准确度在94.8％-107.1％之间,精密度偏差在士6％之内.该方法可成功应用于达比加群酯纳米混悬剂beagle犬的药代动力学研究.纳米混悬剂的达峰浓度和曲线下面积均显著高于对照制剂,表明该制剂可显著提高口服吸收.“,”In this study,a sensitive and rapid LC-MS/MS method was developed and validated to determine dabigatran in plasma of beagle dogs after oral administration of dabigatran etexilate nanosuspension (DABE-NS).The analytes (dabigatran) and sertraline hydrochloride (internal standard,IS) were separated on a Kromasil C18 column using gradient elution consisting of methanol and formate buffer at a flow rate of 0.4 mL/min in 20 min.Detection and quantitation were carried out by multiple reaction monitoring following the transitions:m/z 472.17→289.07 and 305.98,275.00 for dabigatran and IS at positive ion mode,respectively.The calibration curves were linear from 1.0 to 500.0 ng/mL for dabigatran with r =0.9995.The accuracy of each analyte ranged from 94.8％ to 107.1％,and the precision was within 6％.Besides,this method was successfully applied in the investigation of the pharmacokinetic profile of dabigatran in beagle dogs after oral administration of DABE-NS.The maximum concentration and the areas under curves of dabigatran for DABE-NS were significantly higher than those of control formulation,indicating improved oral absorption.