title: Demonstrative validation study employing a packed column pressurized fluid chromatography method that provides assay, achiral impurities, chiral impurity, and IR identity testing for a drug substance.
abstract: Assay development, assay validation, and documentation are reported here for a single packed column pressurized fluid chromatographic/ultraviolet (UV) method that provides: (1) simultaneous detection and quantification for the chiral drug, the chiral impurity and seven achiral impurities; and (2) a Fourier transform infrared (FT-IR) spectrometric identification test result for the Searle drug substance sample, xemilofiban. The separation is achieved in less than 30 min with three columns in tandem and a gradient of CO2-CH3OH. The post-column flow is split between UV (assay) and FT-IR (identification). Precision and accuracy are consistent within figures of merit obtained by liquid chromatographic-ultraviolet assays on analogous drug substances. The reported procedure combines three typical drug substance tests into one test (e.g. chiral impurities, achiral impurities, and infrared identification).
authors.affiliation: Department of Chemistry, Virginia Tech, College of Arts and Sciences, 107 Davidson Hall, Blacksburg, VA 24061-0212, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ashraf-Khorassani
authors.forename: L T
authors.initials: LT
authors.lastname: Taylor
authors.forename: D G
authors.initials: DG
authors.lastname: Williams
authors.forename: D A
authors.initials: DA
authors.lastname: Roston
authors.forename: T T
authors.initials: TT
authors.lastname: Catalano
mesh_terms: D002853:Chromatography, Liquid; D004340:Drug Contamination; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D015203:Reproducibility of Results; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions