Online nanoelectrospray/high-field asymmetric waveform ion mobility spectrometry as a potential tool for discovery pharmaceutical bioanalysis.
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%.
Hatsis
Panos
P
Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals Inc., 35 Landsdowne St, Cambridge, MA 02139, USA. panos.hatsis@novartis.com
Valaskovic
Gary
G
Wu
Jing-Tao
JT
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*
D004364:Pharmaceutical Preparations