Microextraction in packed syringe/liquid chromatography/electrospray tandem mass spectrometry for quantification of olomoucine in human plasma samples

Olomoucine is a purine analogue that selectively inhibits cyclin-dependent kinases. Malfunction of these enzymes has been associated with several diseases, including cancer. Olomoucine was introduced recently into clinical trials. The aim of the present investigation was to develop a simple, fast and sensitive method for the determination of olomoucine in plasma samples. The determination of olomoucine in plasma and urine was performed using micro extraction in packed syringe (MEPS) as sample preparation method on-line with high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). In MEPS, the sampling sorbent was 1 mg polystyrene polymer that was inserted in a 250-mu L syringe. Roscovitine was used as internal standard. The limit of detection (LOD) for olomoucine was 0.5 ng/mL and the lower limit of quantification (LLOQ) was set to 1.0 ng/mL. The accuracy values of quality control samples (QC) were between +/- 15%, and precision (R.S.D.) had a maximum deviation of 10%. The standard curve was obtained within the concentration range 0.5-2000 ng/mL in both plasma and urine. The regression correlation coefficients (R 2) for plasma and urine samples were >= 0.999 for all runs. The present method is miniaturized, fully automated and robust that can be easily used for pharmacokinetic and pharmacodynamic studies of olomoucine. (c) 2005 Elsevier B.V. All rights reserved.