title: Extracting metabolite ions out of a matrix background by combined mass defect, neutral loss and isotope filtration.
abstract: Mass defect, neutral loss and isotope filtration techniques were applied to electrospray ionization mass spectrometry (ESI-MS) data obtained for in vivo and in vitro samples of drug metabolism studies. A combination of these post-acquisition processing techniques was shown to be more powerful than the use of one of these tools alone for the detection in complex matrices of metabolites of candidate drugs with a characteristic isotope pattern (e.g. containing bromine, chlorine, or a high proportion of radiolabeled drug ((12)C/(14)C)) or characteristic neutral losses. In combination with 'all-in-one' data acquisition this methodology is able to perform software-driven constant neutral loss scanning for an unlimited number of mass differences at any time after analysis. Highly selective MS chromatograms were obtained with excellent correlation with their corresponding radiochromatograms.
authors.affiliation: Global Preclinical Development, Johnson & Johnson Pharmaceutical R&D, Turnhoutseweg 30, 2340 Beerse, Belgium. fcuycken@its.jnj.com
authors.forename: Filip
authors.initials: F
authors.lastname: Cuyckens
authors.forename: Rob
authors.initials: R
authors.lastname: Hurkmans
authors.forename: Jose M
authors.initials: JM
authors.lastname: Castro-Perez
authors.forename: Laurent
authors.initials: L
authors.lastname: Leclercq
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mortishire-Smith
mesh_terms: D000465:Algorithms; D000818:Animals; D002247:Carbon Isotopes / Q000302:isolation & purification*; D064687:Diarylquinolines; D004285:Dogs; D005243:Feces / Q000737:chemistry*; D007477:Ions; D010599:Pharmacokinetics; D011804:Quinolines / Q000493:pharmacokinetics*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D002247:Carbon Isotopes; D064687:Diarylquinolines; D007477:Ions; D011804:Quinolines; C493870:bedaquiline