Enantioselective Determination of S- and R-isomers of Ibuprofen in Plasma by Ultra-Performance Liquid Chromatography - Tandem Mass Spectrometry

A new method of enantioselective determination of S- and R-isomers of ibuprofen in human plasma by ultra-performance liquid chromatography with tandem mass spectrometric detection using solid-phase extraction was developed. For enantioselective separation of ibuprofen isomers, a LUX Cellulose-3 chiral chromatographic column was used. Complete separation of the enathiomer peaks is achieved in the isocratic elution conditions with a mobile phase ratio of 0.05% formic acid solution (%): methanol (%) = 30:70 (v/v) and a flow rate of 0.2 mL/min, The mass spectrometric detection was performed at negative ionization mode with multiple reaction monitoring, using the transitions at 205.13 > 161.14 Da and 208.09 > 164.03 Da for ibuprofen enantiomers and deuterated ibuprofen (internal standard), respectively The method validation included the evaluation of the selectivity linearity, lower limit of quantification (LLOQ), within-run and between-run precision and accuracy. The LLOQ for the two enantiomers was 100 ng/mL in plasma. The calibration curves showed good linearity of each enantiomers in the ranges from 100 to 60000 ng/mL. The method was successfully applied to a pharmacokinetic study of ibuprofen enantiomers in human plasma.