GC-MS and GC-MS/MS measurement of ibuprofen in 10-μL aliquots of human plasma and mice serum using [α-methylo- 2 H 3 ]ibuprofen after ethyl acetate extraction and pentafluorobenzyl bromide derivatization: Discovery of a collision energy-dependent H/D isotope effect and pharmacokinetic application to inhaled ibuprofen-arginine in mice.

•Quantitative GC–MS and GC–MS/MS methods for ibuprofen were developed.•Ibuprofen and the internal standard d3-ibuprofen were solvent extracted.•Ibuprofen and d3-ibuprofen were derivatized with pentafluorobenzyl (PFB) bromide.•ECNICI of the PFB esters of Ibuprofen and d3-ibuprofen yields their carboxylates.•In GC–MS/MS collision induces a remarkable H/D isotope effect.