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目的:建立准确、灵敏、可靠的LC-MS法检测大鼠血浆中酒石酸美托洛尔的浓度。方法:血浆样品用乙酸乙酯液-液萃取,内标选用盐酸普萘洛尔,液相色谱柱为ThermoODS-C18(5.0μm,100mm×2.1mm),流动相为含0.1%甲酸的乙腈:甲醇:水(20:20:60,体积比),流速为0.2ml/min;仪器选用Agilent公司1100LC/MSDSL型液相色谱-质谱联用仪,采用电喷雾离子化电离源(ESI),选择性离子监测(SIM)方式进行正离子检测,用于定量分析的离子反应分别为m/z267→268(美托洛尔)和m/z259→260(普萘洛尔)。结果:在本实验条件下,美托洛尔与内标盐酸普萘洛尔分离良好,保留时间分别为1.79和4.01min,0.1～50ng/ml范围内线性关系良好(r2=0.99411),提取回收率均大于80%,日内日间精密度均小于15%(n=5)。结论:该方法快速、准确、灵敏度高,专属性好,可用于酒石酸美托洛尔在大鼠体内药物代谢动力学的研究。
Objective: To establish an accurate, sensitive and reliable LC-MS method for the determination of metoprolol tartrate in rat plasma. Methods: The plasma samples were extracted by liquid-liquid extraction with ethyl acetate and propranolol hydrochloride as internal standard. The column was ThermoODS-C18 (5.0μm, 100mm × 2.1mm) and the mobile phase was acetonitrile containing 0.1% Methanol: water (20:20:60, volume ratio) at a flow rate of 0.2ml / min. The instrument was selected by Agilent 1100LC / MSDSL liquid chromatography-mass spectrometry with electrospray ionization ionization source The positive ion detection was performed by the SIM method, and the ion reaction for quantitative analysis was m / z267 → 268 (metoprolol) and m / z259 → 260 (propranolol). Results: Under the experimental conditions, metoprolol was separated from the internal standard propranolol hydrochloride for a retention time of 1.79 and 4.01 min, respectively, with a good linearity in the range of 0.1-50 ng / ml (r2 = 0.99411) Rates were greater than 80%, intraday and day precision were less than 15% (n = 5). Conclusion: The method is rapid, accurate, sensitive and specific. It can be used to study the pharmacokinetics of metoprolol tartrate in rats.