title: Online nanoelectrospray/high-field asymmetric waveform ion mobility spectrometry as a potential tool for discovery pharmaceutical bioanalysis.
abstract: Nanoelectrospray ionization (nESI) coupled online with high-field asymmetric waveform ion mobility spectrometry (FAIMS) for small molecule analysis in a discovery pharmaceutical setting was examined. A conventional capillary pump, autosampler and nESI source were used to introduce samples directly into the FAIMS device. The FAIMS device was used to separate gas-phase ions on a timescale that was compatible with the mass spectrometer. The capability of the nESI-FAIMS combination to efficiently remove metabolite interferences from the parent drug, and reduce ion suppression effects, was demonstrated. On average, 85% of the signal intensity obtained from a neat sample was preserved in the extracted plasma samples. Standard curves were prepared for several compounds. Linearity was obtained over approximately 3 to 4 orders of magnitude. Comparison of results from nESI-FAIMS with those from conventional LC/MS for a mouse pharmacokinetic study yielded concentration values differing by no more than 30%.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals Inc., 35 Landsdowne St, Cambridge, MA 02139, USA. panos.hatsis@novartis.com
authors.forename: Panos
authors.initials: P
authors.lastname: Hatsis
authors.forename: Gary
authors.initials: G
authors.lastname: Valaskovic
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Wu
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D016014:Linear Models; D051379:Mice; D036103:Nanotechnology / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000097:blood / Q000737:chemistry*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations