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

LC-MS/MS with Chiralcel OD-H chiral column simultaneously determination of four β-blocker enantioners

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,5μm)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.