title: Method development and validation of arene substituted regioisomers in a pharmaceutical candidate by high temperature GC-FID.
abstract: This paper describes the development and validation of a high temperature gas chromatography flame ionization detection (HTGC-FID) method for the purity evaluation of arene substituted regioisomers in a key starting material of a pharmaceutical candidate in Phase 3 studies. The chromatographic conditions of the method employ a (5%-phenyl)-methylpolysiloxane packed column (30m×0.25mm) at a constant flow of 1.0mLmin(-1) with a gradient temperature program from 150°C to 400°C with injector and detector temperatures of 300°C and 340°C, respectively. The calibration curve for the desired product (r=0.9999) was assessed for five points in the range from approximately 1.0μgmL(-1) to 40μgmL(-1). The precision (% RSD) of the method was calculated for six replicate injections and found to be 0.81%. The limits of detection and quantitation were determined to be 0.06 and 0.20μgmL(-1), respectively.
authors.affiliation: Analytical Research and Development, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA. Electronic address: john.j.salisbury@pfizer.com.
authors.forename: John J
authors.initials: JJ
authors.lastname: Salisbury
authors.affiliation: Chemical Research and Development, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Nga M
authors.initials: NM
authors.lastname: Do
authors.affiliation: Chemical Research and Development, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Ragan
mesh_terms: D002138:Calibration; D002849:Chromatography, Gas; D005410:Flame Ionization; D006358:Hot Temperature; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D007202:Indicators and Reagents; D057230:Limit of Detection; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D006841:Hydrocarbons, Aromatic; D007202:Indicators and Reagents
keywords: High temperature gas chromatography; Method Development; Pharmaceutical; Regioisomers; Validation