title: Simultaneous achiral-chiral analysis of pharmaceutical compounds using two-dimensional reversed phase liquid chromatography-supercritical fluid chromatography.
abstract: A new interface was designed to enable the coupling of reversed phase liquid chromatography (RPLC) and supercritical fluid chromatography (SFC). This online two-dimensional chromatographic system utilizing RPLC in the first dimension and SFC in the second was developed to achieve simultaneous achiral and chiral analysis of pharmaceutical compounds. The interface consists of an eight-port, dual-position switching valve with small volume C-18 trapping columns. The peaks of interest eluting from the first RPLC dimension column were effectively focused as sharp concentration pulses on small volume C-18 trapping column/s and then injected onto the second dimension SFC column. The first dimension RPLC separation provides the achiral purity result, and the second dimension SFC separation provides the chiral purity result (enantiomeric excess). The results are quantitative enabling simultaneous achiral, chiral analysis of compounds. The interface design and proof of concept demonstration are presented. Additionally, comparative studies to conventional SFC and case studies of the applications of 2D LC-SFC in pharmaceutical analysis is presented.
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States. Electronic address: cvenkatramani@yahoo.com.
authors.forename: C J
authors.initials: CJ
authors.lastname: Venkatramani
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States. Electronic address: alsayah.mohammad@gene.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Sayah
authors.affiliation: University of Illinois at Chicago, Chicago, IL 60612, United States.
authors.forename: Guannan
authors.initials: G
authors.lastname: Li
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Goel
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States.
authors.forename: James
authors.initials: J
authors.lastname: Girotti
authors.affiliation: Agilent Technologies, Santa Clara, CA 95051, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zang
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States.
authors.forename: Larry
authors.initials: L
authors.lastname: Wigman
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Yehl
authors.affiliation: Small Molecule Analytical Chemistry & Quality Control, Genentech, Inc. So., San Francisco, CA 94080, United States.
authors.forename: Nik
authors.initials: N
authors.lastname: Chetwyn
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations
keywords: 2D LC–SFC; Enatiomeric excess; Liquid chromatography; On-column focusing and trapping columns; Supercritical fluid chromatography