title: Pharmaceutical metabolite profiling using quadrupole/ion mobility spectrometry/time-of-flight mass spectrometry.
abstract: The use of hybrid quadrupole ion mobility spectrometry time-of-flight mass spectrometry (Q/IMS/TOFMS) in the metabolite profiling of leflunomide (LEF) and acetaminophen (APAP) is presented. The IMS drift times (T(d)) of the drugs and their metabolites were determined in the IMS/TOFMS experiments and correlated with their exact monoisotopic masses and other in silico generated structural properties, such as connolly molecular area (CMA), connolly solvent-excluded volume (CSEV), principal moments of inertia along the X, Y and Z Cartesian coordinates (MI-X, MI-Y and MI-Z), inverse mobility and collision cross-section (CCS). The correlation of T(d) with these parameters is presented and discussed. IMS/TOF tandem mass spectrometry experiments (MS(2) and MS(3)) were successfully performed on the N-acetyl-p-benzoquinoneimine glutathione (NAPQI-GSH) adduct derived from the in vitro microsomal metabolism of APAP. As comparison, similar experiments were also performed using hybrid triple quadrupole linear ion trap mass spectrometry (QTRAPMS) and quadrupole time-of-flight mass spectrometry (QTOFMS). The abilities to resolve the product ions of the metabolite within the drift tube and fragment the ion mobility resolved product ions in the transfer travelling wave-enabled stacked ring ion guide (TWIG) demonstrated the potential applicability of the Q/IMS/TOFMS technique in pharmaceutical metabolite profiling.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543. phaccye@nus.edu.sg
authors.forename: Eric C Y
authors.initials: EC
authors.lastname: Chan
authors.forename: Lee Sun
authors.initials: LS
authors.lastname: New
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Yap
authors.forename: Lin Tang
authors.initials: LT
authors.lastname: Goh
mesh_terms: D000082:Acetaminophen / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002853:Chromatography, Liquid; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007555:Isoxazoles / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000077339:Leflunomide; D016014:Linear Models; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure
chemical_list: D007555:Isoxazoles; D000082:Acetaminophen; D000077339:Leflunomide