title: LCMS using a hybrid quadrupole time of flight mass spectrometer for impurity identification during process chemical development of a novel integrase inhibitor.
abstract: LCMS incorporating a quadrupole time of flight mass spectrometer was used to identify impurities found in a chemical process development sample of a novel integrase inhibitor, raltegravir. The combination of accurate mass measurement in full scan mode followed by construction of targeted masses for further MSMS interrogation allowed for the determination of atomic composition and connectivity. The fragmentation pattern of raltegravir was used as a model compound, and the product ion spectra of an impurity was compared to both the model fragmentation pattern and the atomic composition generated in the full scan experiment to deduce a structure.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA. thomas novak@merck.com
authors.forename: T J
authors.initials: TJ
authors.lastname: Novak
authors.forename: N
authors.initials: N
authors.lastname: Grinberg
authors.forename: B
authors.initials: B
authors.lastname: Hartman
authors.forename: S
authors.initials: S
authors.lastname: Marcinko
authors.forename: L
authors.initials: L
authors.lastname: DiMichele
authors.forename: B
authors.initials: B
authors.lastname: Mao
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D019428:HIV Integrase Inhibitors / Q000032:analysis / Q000737:chemistry; D011760:Pyrrolidinones / Q000032:analysis* / Q000737:chemistry; D000068898:Raltegravir Potassium; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium