Effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo / 药学实践杂志

ABSTRACT

Objective To establish a UPLC-MS/MS method for the determination of dexmedetomidine in human plasma and investigate the effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo. Methods Samples were obtained by liquid-liquid extraction. Agilent Eclipse Plus C18 column was used for chromatograph with methanol and 0.1% formic acid-water solution as mobile phase. Flow rate was 0.2 ml/min. The column temperature was 35 ℃, and the MS detection was selected in MRM mode. Results The calibration curves of dexmedetomidine showed good linearity in the ranges of 0.01−10.00 ng/ml. The results of intra and inter-day precisions were both within 15%. The recovery rate was 85.5%−93.1%. Matrix effect was 91.2%−95.6%. Samples remained stable during analysis. Compared with the control group, cmax、AUC(0−t)、AUC(0−∞) and Vz of dexmedetomidine in the patients with obstructive jaundice were increased by 63.4%, 78.9, 66.4%, 82.5%, respectively (P<0.01). CLz was decreased by 42.1%. Conclusion This method is accurate, sensitive and reproducible. It is suitable for dexmedetomidine assay in human plasma. The elimination rate of dexmedetomidine is slower in obstructive jaundice.