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.
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).
Ashraf-Khorassani
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M
Department of Chemistry, Virginia Tech, College of Arts and Sciences, 107 Davidson Hall, Blacksburg, VA 24061-0212, USA.
Taylor
L T
LT
Williams
D G
DG
Roston
D A
DA
Catalano
T T
TT
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
D004364:Pharmaceutical Preparations; D012996:Solutions