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%. Copyright © 2009 John Wiley & Sons, Ltd.