title: Supercritical fluid chromatography for GMP analysis in support of pharmaceutical development and manufacturing activities.
abstract: Supercritical fluid chromatography (SFC) has long been a preferred method for enantiopurity analysis in support of pharmaceutical discovery and development, but implementation of the technique in regulated GMP laboratories has been somewhat slow, owing to limitations in instrument sensitivity, reproducibility, accuracy and robustness. In recent years, commercialization of next generation analytical SFC instrumentation has addressed previous shortcomings, making the technique better suited for GMP analysis. In this study we investigate the use of modern SFC for enantiopurity analysis of several pharmaceutical intermediates and compare the results with the conventional HPLC approaches historically used for analysis in a GMP setting. The findings clearly illustrate that modern SFC now exhibits improved precision, reproducibility, accuracy and robustness; also providing superior resolution and peak capacity compared to HPLC. Based on these findings, the use of modern chiral SFC is recommended for GMP studies of stereochemistry in pharmaceutical development and manufacturing.
authors.affiliation: Department of Process & Analytical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. Electronic address: michael.hicks@merck.com.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Hicks
authors.affiliation: Department of Process & Analytical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Regalado
authors.affiliation: Department of Process & Analytical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Tan
authors.affiliation: Department of Process & Analytical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Process & Analytical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Welch
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000639:trends; D025924:Chromatography, Supercritical Fluid / Q000379:methods* / Q000639:trends; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D004345:Drug Industry / Q000379:methods* / Q000639:trends
keywords: Chiral stationary phases; Enantiomers; GMP SFC; Method validation; Pharmaceutical impurities; Supercritical fluid chromatography