药浴暴露下阿维菌素在异育银鲫体内蓄积和消除规律

Accumulation and elimination of Avermectin in Carassius auratus gibelio following medicated bath exposure

采用UPLC-MS/MS法研究了2μg·L-1三次连续水体药浴和6μg·L-1一次性水体药浴条件下阿维菌素在水体中消除、在异育银鲫(Carassius auratus gibelio)体内蓄积和消除变化规律。结果显示,两种药浴暴露方式下阿维菌素在水体中消除呈一级指数衰退消除,消除半衰期(t1/2)均为63 h,240 h时浓度下降到0.5μg·L-1以下。阿维菌素在异育银鲫血浆和肌肉中的含量均呈先升高后下降的趋势,血浆中药物浓度远高于肌肉中的含量。2μg·L-1连续三次药浴组和6μg·L-1一次药浴组血药峰浓度(Cmax)分别为34.97、66.62μg·L-1,其曲线下面积(AUC0-t)分别为9 871.2μg·L-1·h和18 119.6μg·L-1·h;两组药浴肌肉中达峰浓度分别4.42μg·kg-1和15.80μg·kg-1,其AUC0-t分别为641.9μg·kg-1·h和4 271.0μg·kg-1·h。与2μg·L-1连续三次药浴组相比,6μg·L-1一次药浴组阿维菌素在血浆和肌肉中的蓄积作用更加显著。以10μg·kg-1作为阿维菌素在异育银鲫肌肉中最大残留限量,选择95%的置信区间计算异育银鲫肌肉组织中休药期,本研究中2μg·L-1连续三次药浴组肌肉的休药期为295.4 h,6μg·L-1一次药浴组肌肉的休药期为454.5 h。

In this paper,ultra high performance liquid chromatography tandem mass spectrometer （UPLC-MS/MS） was used to detect Avermectin in water and biological samples based on the optimized pretreatment.Using this detection method,the elimination of Avermectin in water,the accumulation and elimination of Avermectin in Carassius auratus gibelio were studied following bath exposure at three consecutive doses of 2 μg · L-1 every other day and at a single dose of 6 μg · L-1to investigate the impact on aquatic animals after bath exposure and provide basic data for safety evaluation of Avermectin in aquaculture.The limits of detection（LOD） in water,plasma and muscle were 0.03 μg · L-1,0.15 iμg · kg-1 and 0.2 μg · kg-1,respectively,and the limits of quantitation（LOQ） were 0.10 μg · L-1,0.4 μg · L-1,0.5 μg · kg-1,respectively.The linear range in water,plasma and muscle were 0.1-50 μg · L-1,0.4-75 μg · L-1 and 0.5-50 μg · kg-1,respectively,which showed good linearity,and the average recoveries were between 85％ -115％.The detection method could meet the normal residual analysis requirements.Results of bath exposure showed that the Avermectin in water was eliminated by first-order exponential rate and half-life times （t1/2） were 63 h for both three consecutive exposure and the single exposure.The Avermectin concentrations in water were below 0.5 μg · L-1 in 240 h.The Avermectin concentrations in plasma and muscle increased at first following bath exposure and then decreased after peak time.The avermectin concentrations in plasma were significantly higher than that in muscle.The peak concentration （Cmax） of plasma following three consecutive dosage and a single dosage were 34.97 μg · L-1 and 66.62 μg · L-1,respectively; while the area under the concentration-time curve （AUC0-1）were 9 871.2 tμg· L-1 · h and 18 119.6 tμg· L-1 · h,respectively.The Cmax in muscle were 4.42 μg · kg-1 and 15.80 μg · kg-1,respectively,and AUC0-1 were 641.9 μg· kg-1 · h and 4 271.0 μg · kg-1 · h,respectively.Accumulation of Avermectin in blood and muscle after a single exposure was more significant than that following three consecutive exposure.Regarding 10 μg · kg-1 as the maximum residue limit （MRL） of Avermectin in muscle,the withdrawal period of Avermectin in muscle was 295.4 h and 454.5 h for three consecutiveexposure of 2 μg · L-1 and single exposure of 6 tμg · L-1 by the 95％ confidence interval analysis.These results provided guiding significance for fishery drugs usage and establishment of withdrawal period in aquaculture.