Determination of some antiallergic drugs in human plasma by direct-injection high-performance liquid chromatography-tandem mass spectrometry

A detailed procedure for analysis of four antiallergic drugs, ketotifen, olopatadine, cetirizine, and ibudilast, in human plasma by high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS-MS) using a new polymer column (MSpak GF), which enables direct injection of crude biological samples, is presented. The protein and/or macromolecule matrix compounds were first eluted from the column, while the drugs were retained on the polymer stationary phase. The analytes retained on the column were then eluted into an acetonitrile-rich mobile phase using a gradient separation technique. All compounds showed base peaks due to [M + H]+ ions by HPLC-MS with positive ion electrospray ionization, and the product ions were produced from each [M + H]+ ion by HPLC-MS-MS. Quantification was made by selected reaction monitoring. The recoveries of the four antiallergic drugs spiked into plasma were 51.7-95.5%. The regression equations for the four antiallergic drugs showed excellent linearity in the range of 1-100 ng/ml of plasma. The detection limit was 0.5 ng/ml for all compounds. The intraday and interday precisions for the drugs in plasma were not greater than 9.5%. The data obtained from actual determination of the antiallergic drugs in human plasma after their oral administration are also presented for validation of the method. © Japanese Association of Forensic Toxicology and Springer-Verlag 2006.