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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C18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 m L/min。达比加群[M+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/m L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±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。
This study established a rapid and sensitive quantitative method for the determination of plasma concentrations of dabigatran in beagle dogs after oral administration of dabigatran etexilate nanosuspension. Liquid-mass spectrometry / mass spectrometry was performed on reversed-phase C18 column with gradient elution with methanol-formic acid as mobile phase and sertraline hydrochloride as internal standard at a flow rate of 0.4 mL / min. Dabigatran [M + H] + m / z 472.17 → 289.07, sertraline [M + H] + m / z 305.98 → 275.00, positive ion mode, mass spectrometry multiple reaction monitoring scanning method for the determination of dabigatran concentration. The results showed that dabigatran had a good linearity (r = 0.9995) over the concentration range of 1.0-500 ng / mL, with accuracies of 94.8% -107.1% and precision within ± 6%. The method can be successfully applied to the pharmacokinetics study of dabigatran etexilate beagle dogs. Both the peak concentration and the area under the curve of the nanosuspension were significantly higher than that of the control formulation, indicating that the formulation can significantly improve oral absorption.