Effective methodologies for enantiomeric separations of 150 pharmacology and toxicology related 1°, 2°, and 3° amines with core-shell chiral stationary phases

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 155; pp. 70 - 81
• Main Authors: Hellinghausen, Garrett, Roy, Daipayan, Lee, Jauh T., Wang, Yadi, Weatherly, Choyce A., Lopez, Diego A., Nguyen, Kate A., Armstrong, John D., Armstrong, Daniel W.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05-06-2018
• Subjects: Controlled substance; Cyclodextrin; Cyclofructan; Enantiomer separations; Macrocyclic glycopeptide; Superficially porous particles (SPP); Superficially porous particles (SPP); Cyclodextrin; Controlled substance; Cyclofructan; Enantiomer separations; Macrocyclic glycopeptide
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2018.03.032

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•Rapid method development for optimized enantiomeric separations of 150 amines.•Biological compatible MS analysis of 150 amines.•Complementary separations with macrocyclic chiral selectors.•High-throughput chiral separations with core-shell chiral stationary phases.•Single LC–MS chiral separation of 18 illicit substances in 35 min.
Core-shell particles (superficially porous particles, SPPs) have been proven to provide high-throughput and effective separations of a variety of chiral molecules. However, due to their limited commercialization, many separations have not been reported with these stationary phases. In this study, four SPP chiral stationary phases (CSPs) were utilized for the enantiomeric separation of 150 chiral amines. These amines encompass a variety of structural and drug classes, which are particularly important to the pharmaceutical industry and in forensics. This comprehensive evaluation demonstrates the power of these CSPs and the ease of method development and optimization. The CSPs used in this study included the macrocyclic glycopeptide-based CSPs (VancoShell and NicoShell), the cyclodextrin-based CSP (CDShell-RSP), and the cyclofructan-based CSP (LarihcShell-P). These CSPs offered versatility for a variety of applications and worked in a complementary fashion to baseline separate all 150 amines. The LarihcShell-P was highly effective for separating primary amines. VancoShell, NicoShell, and CDShell-RSP were useful for separating all types of amines. These CSPs are multi-modal and can be utilized with mass spectrometry compatible solvents. Eighteen racemic controlled substances were simultaneously baseline separated in a single liquid chromatography–mass spectrometry (LC–MS) analysis. Details in high-performance liquid chromatography (HPLC) parameters will be discussed as well as the improved chromatographic performance afforded by the SPP CSPs.