title: Development of LC chiral methods for neutral pharmaceutical related compounds using reversed phase and normal phase liquid chromatography with different types of polysaccharide stationary phases.
abstract: The enantioselectivity of a collection of neutral pharmaceutical compounds on six different types of polysaccharide chiral stationary phases (CSPs), Chiralpak AD (and AD-RH), Chiralcel OD (and OD-RH), Chiralpak OJ (and OJ-R), Chiralcel AS (and AS-RH), Sepapak-2 and Sepapak-4 are compared using reversed phase (RPLC) and normal phase liquid chromatography (NPLC). Screening strategies for maximizing the probability of achieving an initial chiral separation hit for neutral compounds using both RPLC and NPLC are described. Further method optimizations are demonstrated by modifying parameters such as organic modifier composition, eluent pH or CSP particle size. Several practical examples of the application of chiral methods for the study of synthetic reaction mixtures are presented. The most critical validation aspects, including limit of detection, specificity, and ruggedness, are also briefly presented.
authors.affiliation: Merck Research Laboratories, Merck & Co Inc, Rahway, NJ 07065, USA. lili_zhou@merck.com
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Chris
authors.initials: C
authors.lastname: Welch
authors.forename: Clair
authors.initials: C
authors.lastname: Lee
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gong
authors.forename: Vincent
authors.initials: V
authors.lastname: Antonucci
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Ge
mesh_terms: D002853:Chromatography, Liquid; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011134:Polysaccharides / Q000737:chemistry*; D015203:Reproducibility of Results; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D011134:Polysaccharides; D012997:Solvents