A HIGHLY SENSITIVE METHOD FOR THE QUANTIFICATION OF DEXMEDETOMIDINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

摘要

INTRODUCTION: Dexmedetomidine is a lipophilic imidazole derivative with a high affinity for alpha-2 adrenergic receptors, which exhibits sedative, analgesic-sparing and sympatholytic properties. A highly sensitive LC-MS/MS method has been developed and validated for the quantitation of dexmedetomidine in human plasma. METHODS: Sample preparation of 100 μL plasma was performed by liquid-liquid extraction using methyl tert-butyl ether and 5 N ammonium hydroxide. The separation of dexmedetomidine and IS was achieved on a Luna CN column (2.1 × 100 mm, 3 μm, Phenomenex, USA) with a mobile phase consisting of distilled water and acetonitrile containing 0.1% formic acid (40:60, v/v). Positive electrospray ionization in multiple reaction monitoring (MRM) mode was employed. The MRM was based on m/z transitions of 201.16>95.03 for dexmedetomidine and 161.11>91.10 for tolazoline (IS). RESULT: The proposed method has been validated with linear range of 0.005 - 2 ng/mL. The between-run precision and accuracy of the QC samples were found to be within the range of 3.710-7.771% and 94.30-107.5%, respectively. Recoveries at concentrations of 0.015, 0.15 and 1.5 ng/mL were all greater than 80%, and matrix effects were within 15%. Dexmedetomidine was stable in human plasma at room temperature for 19 h and at -80°C for 197 days, in an auto-sampler at 4°C for 24 h, and during 3 freeze-thaw cycles. CONCLUSION: This validated LC-MS/MS method provides a highly sensitive and reliable method for quantification of dexmedetomidine in human plasma.