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Parallel SFC/MS‐MUX screening to assess enantiomeric purity
Author(s) -
Laskar Derek B.,
Zeng Lu,
Xu Rongda,
Kassel Daniel B.
Publication year - 2008
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20553
Subject(s) - chemistry , enantiomer , elution , chromatography , stereocenter , supercritical fluid chromatography , mass spectrometry , resolution (logic) , supercritical fluid , enantiomeric excess , analytical chemistry (journal) , enantioselective synthesis , high performance liquid chromatography , organic chemistry , catalysis , artificial intelligence , computer science
Enantiomeric excess ( ee ) was evaluated for two internally synthesized compound libraries using a high‐throughput automated, intelligent four‐channel parallel supercritical fluid chromatography/mass spectrometry system equipped with a multiplexed ion source interface (SFC/MS‐MUX). The two libraries contained compounds spanning a wide range of enantiomeric ratios with structurally diverse chemical scaffolds and stereogenic centers. The system analyzed each sample simultaneously against four chiral columns using up to six organic modifiers. Enhancements to our previously published parallel supercritical fluid chromatography/mass spectrometry system were implemented to address the challenges associated with automated trace enantiomer identification and quantitation. A reversal of enantiomer elution order was observed for several samples across multiple CSPs and modifiers. The relationship between elution order and % ee accuracy is presented for compounds exhibiting high, middle and low % ee values. Despite incidences in which the minor enantiomer eluted prior to the major enantiomer with less than baseline resolution, the overall % ee was in agreement with separations in which full baseline resolution was achieved. The methods presented here demonstrate the value and utility of high‐throughput ee determinations to support drug discovery and development programs. Chirality, 2008. © 2008 Wiley‐Liss, Inc.