Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes E. Str. 9, H-1085 Budapest, Hungary.
Department of General and Inorganic Chemistry, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gh. Marinescu 38, RO-540139 Targu Mures, Romania.
Molecules. 2021 Dec 24;27(1):111. doi: 10.3390/molecules27010111.
The enantioseparation of four phthalimide derivatives (thalidomide, pomalidomide, lenalidomide and apremilast) was investigated on five different polysaccharide-type stationary phases (Chiralpak AD, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) using neat methanol (MeOH), ethanol (EtOH), 1-propanol (PROP), 2-propanol (IPA) and acetonitrile (ACN) as polar organic mobile phases and also in combination. Along with the separation capacity of the applied systems, our study also focuses on the elution sequences, the effect of mobile phase mixtures and the hysteresis of retention and selectivity. Although on several cases extremely high resolutions ( > 10) were observed for certain compounds, among the tested conditions only Chiralcel OJ-H column with MeOH was successful for baseline-separation of all investigated drugs. Chiral selector- and mobile-phase-dependent reversals of elution order were observed. Reversal of elution order and hysteresis of retention and enantioselectivity were further investigated using different eluent mixtures on Chiralpak AD, Chiralcel OD and Lux Amylose-2 column. In an IPA/MeOH mixture, enantiomer elution-order reversal was observed depending on the eluent composition. Furthermore, in eluent mixtures, enantioselectivity depends on the direction from which the composition of the eluent is approached, regardless of the eluent pair used on amylose-based columns. Using a mixture of polar alcohols not only the selectivities but the enantiomer elution order can also be fine-tuned on Chiralpak AD column, which opens up the possibility of a new type of chiral screening strategy.
研究了五种不同多糖型固定相（Chiralpak AD、Chiralpak AS、Lux Amylose-2、Chiralcel OD 和 Chiralcel OJ-H）上四种邻苯二甲酰亚胺衍生物（沙利度胺、泊马度胺、来那度胺和阿普斯特）的对映体分离。使用纯甲醇（MeOH）、乙醇（EtOH）、1-丙醇（PROP）、2-丙醇（IPA）和乙腈（ACN）作为极性有机溶剂相，以及它们的混合物作为流动相。除了应用系统的分离能力外，我们的研究还侧重于洗脱顺序、流动相混合物的影响以及保留和选择性的滞后。尽管在某些情况下，对于某些化合物观察到了极高的分辨率（>10），但在所测试的条件下，只有 Chiralcel OJ-H 柱和 MeOH 成功地实现了所有研究药物的基线分离。观察到了手性选择剂和流动相依赖性的洗脱顺序反转。在手性固定相 AD、Chiralcel OD 和 Lux Amylose-2 柱上，使用不同的洗脱混合物进一步研究了洗脱顺序和保留及对映选择性的滞后反转。在 IPA/MeOH 混合物中，取决于洗脱剂组成观察到对映体洗脱顺序反转。此外，在洗脱混合物中，对映选择性取决于从哪个方向接近洗脱剂的组成，而与用于基于直链淀粉的柱的洗脱剂对无关。使用极性醇混合物不仅可以调整 Chiralpak AD 柱上的选择性，还可以调整对映体的洗脱顺序，这为新的手性筛选策略开辟了可能性。
