关键词: 己烯雌酚, 双烯雌酚, 泥鳅, 药物代谢动力学, 超高效液相色谱-串联质谱法

Abstract:

Tissue distribution and pharmacokinetics of diethylstilbestrol and its metabolite dienestrol in plasma, muscle and liver
of Misgurnus anguillicaudatus under laboratory conditions using single oral administration were studied by ultra-performance
liquid chromatogram tandem mass spectrometry in this work. After a single oral administration with diethylstilbestrol at 0.1,
1.0 and 10.0 mg/kg, diethylstilbestrol concentrations in plasma, muscle and liver versus time were well described by a twodepartment
open model with first-order absorption. For example, after single oral administration at 1.0 mg/kg, the concentration
of diethylstilbestrol in liver was highest, followed successively by that in muscle and plasma. The average elimination speed was
22.46, 3.32 and 5.05 μg/(kg·h) in plasma, muscle and liver, respectively. Diethylstilbestrol was not detected at 6, 72 and 120 h after
oral administration. The changes in dienestrol concentrations were similar those with diethylstilbestrol. Dienestrol concentration
in plasma, muscle and liver reached a peak at 1, 4 and 4 h, respectively, after oral administration, and was not detected at 6, 72
and 96 h after administration, which was shorter than that of diethylstilbestrol. DAS 2.0 pharmacokinetic parameter calculation
program was used to process the data and calculate the relevant pharmacokinetic parameters. The results indicated that the area
under concentration-time curve (AUC) differed greatly in plasma, muscle and liver and these tissues had different accumulation
capabilities. Diethylstilbestrol was eliminated fast. Distribution was dispersed and elimination was fast. Under the experimental
conditions, the recommended withdrawal periods were 3, 5 and 5 d respectively. When the water temperature was higher than the
experimental conditions, the withdrawal period could be shortened and extended at lower water temperature. The concentrations
versus time curves of diethylstilbestrol in Misgurnus anguillicaudatus provided useful information for studying decontamination of
Misgurnus anguillicaudatus that had diethylstilbestrol contamination.

Key words: diethylstilbestrol, dienestrol, Misgurnus anguillicaudatus, pharmacokinetics, ultra performance liquid chromatogram tandem-mass spectrometry