Determination of dexmedetomidine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a pharmacokinetic study.

A rapid, sensitive and selective high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method (HPLC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine (DMED) in human plasma. Dexmedetomidine and the internal standard (ondansetron) were extracted in a single step with diethyl-ether from 1.0 mL of alkalinized plasma. The mobile phase was a mixture of acetonitrile and 0.5% formic acid solution (30:70, v/v) at a flow rate of 0.2 mL min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer in the selected reaction monitoring (SRM) mode using the respective [M+H]+ ions m/z 201.0-->95.1 for DMED and m/z 294.1-->170.1 for the IS. The assay exhibited a linear dynamic range of 5-5000 pg mL(-1) with the correlation coefficient above 0.9995. The lower limit of quantification (LLOQ) was 5 pg mL(-1) with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated HPLC-MS/MS method has been successfully applied to study the pharmacokinetics of three level doses of DMED in Chinese healthy volunteers.

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