Chiralcel_OD-H手性柱液相色谱串联质谱法同时拆分4个β-受体阻滞剂

目的: 建立手性固定相液相色谱串联质谱(LC-MS/MS) 同时分离4个β受体阻滞剂的方法。 方法: 以Chiralcel OD-H(250 mm×4.6 mm,5 μm)为手性柱,通过电喷雾离子化(ESI),采用多反应检测(MRM)方式进行正离子检测, 普萘洛尔、美托洛尔、阿替洛尔、比索洛尔检测离子分别为m/z 260.2→116.0,m/z 268.4→116.0,m/z 267.2→145.0,m/z 326.2→116.0,在23 min 内同时完成4个对映体的分离。 结果: 考察了流动相组成、柱温及流速对拆分的影响,并优化了实验条件,最终获得同时分离4个β受体阻滞剂的LC-MS/MS方法。针对药物的结构特点和固定相的种类,探讨了手性分离机理。 结论: 本方法很大程度上提高了分离效率,具有简便、高效及重复性好等特点,可用于该类药物的常规及生物样品分析。

Objective: To develop a chiral stationary phase liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determination of four β-blockers. Methods: Chromatographic separation was achieved on a Chiralcel OD-H (250 mm×4.6 mm,5 μm) chiral column with a run time of 23.0 min.ESI⁺ was performed in multiple reaction monitoring mode (MRM),using the transitions of m/z 260.2→116.0 for propranolol,m/z 268.4→116.0 for metoprolol,m/z 267.2→145.0 for atenolol,and m/z 326.2→116.0 for bisoprolol. Results: The effects of mobile phase formulation,column temperature,and flow rate on the chiral separation of the four β-blocking agents were investigated,and optimal conditions were obtained.The possible mechanism of chiral separation was discussed based on the structural characteristics of the agents and the sorts of stationary phase. Conclusion: The method developed in our study greatly improved the separation efficiency.It is simple,efficient and with good reproducibility,which can be used for routine and biological specimen analysis of β-blocking enantiomers.