BMS-986142 is a Bruton's tyrosine kinase inhibitor under development to treat several disease types. The compound contains three chiral elements: one chiral center and two chiral axes, resulting in three potential atropisomeric impurities in its drug substance and drug products. Separation of BMS-986142 atropisomers has been successfully achieved on an achiral polar-embedded C18 column in reversed-phase liquid chromatography (RPLC) and on polysaccharide-based chiral columns in RPLC and supercritical fluid chromatography (SFC). Compared to the RPLC chiral separation, the SFC atropisomeric separation on a sub-2 μm immobilized cellulose-based column is much more efficient and environmentally friendly. The analysis time in SFC was reduced by 8-fold compared to that in RPLC, and the method sensitivity in SFC on the sub-2 μm chiral column in 3.0 mm I.D. was 2 to 4-fold better than that on 3 μm chiral columns in 4.6 mm I.D.. Furthermore, our study suggests that the contribution to band broadening from the extra column volume (ECV) of modern commercial SFC instrument was not negligible for a 3.0 mm I.D. × 100 mm column packed with 1.6 μm particles. This result reaffirms that there is a great need for further improvement of SFC instrument design in order to realize the full theoretical efficiency of both sub-2 μm achiral and chiral columns.

BMS-986142是一种正在开发中的布鲁顿酪氨酸激酶抑制剂，可以治疗多种疾病。该化合物包含三个手性元素：一个手性中心和两个手性轴，在其药物和药物产品中产生三种潜在的阻转异构杂质。BMS-986142阻转异构体的分离已在反相液相色谱（RPLC）中的非手性极性嵌入C18色谱柱以及RPLC和超临界流体色谱（SFC）中的基于多糖的手性色谱柱上成功实现。与RPLC手性分离相比，亚2μm固定化纤维素基色谱柱上的SFC阻转异构体分离效率更高且对环境友好。与RPLC相比，在SFC中的分析时间减少了8倍，在亚3μm手性柱上SFC中的方法灵敏度降低了3。0 mm内径比4.6 mm内径的3μm手性色谱柱好2到4倍。此外，我们的研究表明，对于装有1.6μm颗粒的3.0 mm ID×100 mm色谱柱，现代商业SFC仪器的额外色谱柱体积（ECV）对谱带展宽的贡献不可忽略。该结果证实，迫切需要进一步改进SFC仪器设计，以实现亚2μm非手性和手性色谱柱的全部理论效率。