Determination of dexmedetomidine by UHPLC-MS/MS and its application to evaluate the effect of dexmedetomidine concentration on the target-controlled infusion concentration of propofol

The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used in the field of anaesthesiology. This study aimed to develop and validate a rapid, simple and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of DEX in human plasma. The method was applied to evaluate the effect of DEX concentration on the target-controlled infusion (TCI) concentration of PPF. Analytes were separated on a Waters XTERRA (R) MS C18 column with a mobile phase of acetonitrile-methanol-water containing 0.1% formic acid and 5 mM ammonium acetate (70:10:20, v/v/v) at a flow-rate of 0.3 mL/min. Mass spectrometry was performed in the positive selection reaction monitoring mode. The 201.12 -> 95.12 and 515.29 -> 275.68 mass transitions of DEX and IS (telmisartan), respectively, were monitored. The calibration curve of DEX was linear over the concentrations of 0.1-10 ng/mL. The intra-batch and inter-batch precisions of quality control samples were less than 10.05% and had accuracies of less than 6.25%. The newly developed method was successfully applied to quantify the DEX concentrations of plasma samples from 34 patients who were co-medicated with DEX prior to receiving anaesthesia by PPF. Results showed that comedication with DEX could reduce the requirements of PPF. Specifically, it was firstly found that the concentration of DEX is negatively correlated with the TCI concentration of PPF at the time of loss of consciousness. (C) 2018 Published by Elsevier B.V.