title: Determination of arylamines and aminopyridines in pharmaceutical products using in-situ derivatization and liquid chromatography-mass spectrometry.
abstract: Arylamines and aminopyridines form a class of potentially genotoxic impurities (PGIs) that can be present at trace levels in active pharmaceutical ingredients (APIs). A generic method was developed that allows the analysis of a selected set of these solutes at sub-ppm level relative to the drug substance. A highly concentrated solution of the pharmaceutical compound is analyzed by LC-MS using a single quadrupole mass spectrometer in the selected ion monitoring (SIM) mode. Since a number of target compounds show little or no retention in the reversed-phase LC setup, a fast and simple derivatization procedure using hexylchloroformate was applied. The amide derivatives of the PGI result in a higher molecular weight (more specific ion for SIM) and better chromatographic behavior. The methodology, consisting of a dual run on respectively a non-derivatized and a derivatized sample, was validated and applied to a selection of pharmaceutical substances. The method was found to be sufficiently sensitive and robust and is applicable in a QA/QC environment.
authors.affiliation: Research Institute for Chromatography, Kortrijk, Belgium.
authors.forename: Gerd
authors.initials: G
authors.lastname: Vanhoenacker
authors.forename: Emmie
authors.initials: E
authors.lastname: Dumont
authors.forename: Frank
authors.initials: F
authors.lastname: David
authors.forename: Andrew
authors.initials: A
authors.lastname: Baker
authors.forename: Pat
authors.initials: P
authors.lastname: Sandra
mesh_terms: D000588:Amines / Q000032:analysis* / Q000737:chemistry; D000631:Aminopyridines / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D013058:Mass Spectrometry; D009153:Mutagens / Q000737:chemistry; D010404:Penicillin V; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results
chemical_list: D000588:Amines; D000631:Aminopyridines; D009153:Mutagens; D004364:Pharmaceutical Preparations; D010404:Penicillin V