Comparative Chiral Separation of Thalidomide Class of Drugs Using Polysaccharide-Type Stationary Phases with Emphasis on Elution Order and Hysteresis in Polar Organic Mode

Abstract

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 (Rs > 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.

Chirality in Organic and Mineral Systems: A Review of Reactivity and Alteration Processes Relevant to Prebiotic Chemistry and Life Detection Missions

“…In addition to existing instruments, the development of new instruments or instrument capabilities to detect chirality in spaceflight is a necessary component in the search for signs of past life. Advancements in the fields of organic separation (e.g., [500][501][502][503][504]) and detection through mass spectrometry [505,506] are needed to enhance the field of chiral separation on spaceflight missions. Refinement of traditional chiral separation and detection methods as well as the development of new analytical strategies to investigate chiral organics [407,420,[507][508][509] and minerals [510] should be prioritized.…”

Chiral Separation of Apremilast by Capillary Electrophoresis Using Succinyl-β-Cyclodextrin—Reversal of Enantiomer Elution Order by Cationic Capillary Coating

“…For this drug, the more potent S-enantiomer is marketed; therefore, the determination of the R-antipode is a requirement [7,8]. Although several chromatographic methods are described or at least mentioned for the achiral [9,10] and chiral separation of apremilast [11][12][13][14][15][16], based on the authors' knowledge, enantioseparation of APR with capillary electrophoresis was not yet described. marketed; therefore, the determination of the R-antipode is a requirement [7,8].…”

Enantioseparation of syn- and anti-3,5-Disubstituted Hydantoins by HPLC and SFC on Immobilized Polysaccharides-Based Chiral Stationary Phases

“…The chiral stationary phases (CSPs) most commonly used are based on silica coated with chiral polysaccharide derivatives, tris(carbamates) or tris(esters) of amylose or cellulose [36]. These coated CSPs are able to resolve a large variety of structurally different compounds [37,38] and are widely used in HPLC and SFC [39]. These CSPs can only be used with a limited range of solvents as mobile phases such as hydrocarbons, alcohols, acetonitrile (ACN), or hydrocarbon/alcohol and ACN/alcohols mixtures [40].…”