梗阻性黄疸对患者体内右美托咪定药动学的影响

目的建立超高效液相色谱-串联质谱法测定人血浆右美托咪定的浓度,评价梗阻性黄疸对患者体内右美托咪定药动学参数的影响。方法样品经液-液萃取后测定,色谱柱为Agilent Eclipse Plus C18,流动相为甲醇?0.1%甲酸水溶液,流速为0.2 ml/min,柱温为35℃,质谱检测采用动态多反应离子检测模式。结果人血浆中右美托咪定在0.01~10.00 ng/ml浓度范围内线性关系良好,日内和日间精密度均小于15.00%,提取回收率为85.5%~93.1%,基质效应为91.2%~95.6%,样品在分析期间稳定性良好。与对照组相比,梗阻性黄疸患者体内右美托咪定药动学参数cmax、AUC(0?t)、AUC(0?∞)和Vz分别增加63.4%、78.9%、66.4%、82.5%;CLz降低42.1%。结论该方法结果准确,灵敏度高,重现性好,适用于检测人血浆右美托咪定的浓度;梗阻性黄疸患者体内右美托咪定消除减慢。

Effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo

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.