Enantioselective determination of ibuprofen in plasma by high-performance liquid chromatography-electrospray mass spectrometry

The enantioselective analysis of ibuprofen (IBU), a chiral nonsteroidal anti-inflammatory drug, in human plasma was carried out by high-performance liquid chromatography (HPLC)-mass spectrometry (LC-MS-MS). The plasma samples were prepared by liquid-liquid extraction using hexane:ethyl acetate (8:2, v/v). The HPLC chiral resolution of IBU was obtained using a chiral stationary phase based on a tris-(3,5-dimethylphenylcarbamate) amylose derivative, under reversed phase conditions (CHIRALPAK AD-RH column), using a mobile phase consisting of methanol:water (8:2, v/v), containing 0.1% of an aqueous solution of phosphoric acid at pH 2, at a flow rate of 0.6 ml/min. A make-up liquid of 4.5% (w/v) NH4OH aqueous solution was used to assure optimum electrospray ionization in the negative mode. The coefficients of variation and deviation from nominal values were lower than 15% for both within- and between-day assays. The quantitation limit was 0.12 mug/ml and the linear range was 0.12-90.0 mug/ml for both enantiomers. The method proved to be suitable for single dose pharmacokinetic studies. (C) 2003 Elsevier B.V. All rights reserved.