Mitrowska Kamila, Pekala Agnieszka, Posyniak Andrzej
a Department of Pharmacology and Toxicology , National Veterinary Research Institute , Pulawy , Poland.
Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015;32(6):841-8. doi: 10.1080/19440049.2015.1036320. Epub 2015 Apr 24.
Tissue distribution and residue depletion of metronidazole (MNZ) was studied in rainbow trout (Oncorhynchus mykiss) following oral administration of MNZ in feed at the average dose of 25 mg kg(-1) body weight day(-1) for 7 days at 11 ± 2°C. The MNZ concentration in feed was 0.25% while daily feed intake was 1% of body weight. The concentrations of MNZ and its main metabolite, hydroxymetronidazole (MNZOH), in fish tissues were determined by LC-MS/MS. The drug was well distributed in tissues with maximum concentrations on day 1 post-administration. At this time, the mean MNZ concentrations in muscle, skin, kidney, liver and gill were 14,999, 20,269, 15,070, 10,102 and 16,467 µg kg(-1) respectively. MNZ was converted into MNZOH with the ratio of MNZOH:MNZ up to 7% in all fish tissues throughout the withdrawal period. This shows that MNZ itself is the main residue in rainbow trout. MNZ was detected at the level close to the decision limit (0.20 µg kg(-1)) in muscle, skin and muscle with adhering skin up to 42 days, while in kidney, liver and gill it was up to 28 days post-administration. MNZOH was eliminated more rapidly from fish tissues and it was present in muscle alone up to 21 days. The elimination half-lives of MNZ and MNZOH in rainbow trout tissues were 1.83-2.53 and 1.24-2.12 days, respectively. When muscle without skin was analysed, higher MNZ and MNZOH concentrations were detected, and for a longer period of time, than in muscle with adhering skin. Thus muscle alone could be more appropriate for the effective residue control of MNZ in rainbow trout. For the same reason, it is also essential to ensure direct cooling immediately after sampling, since MNZ and its metabolite degrade in fish muscle and skin stored in non-freezing conditions.
在11±2°C条件下，以平均剂量25毫克/千克体重·天的甲硝唑（MNZ）拌入饲料中，连续7天投喂虹鳟（Oncorhynchus mykiss），研究了MNZ在虹鳟体内的组织分布和残留消除情况。饲料中MNZ浓度为0.25%，日摄食量为体重的1%。采用液相色谱-串联质谱法测定鱼组织中MNZ及其主要代谢产物羟基甲硝唑（MNZOH）的浓度。药物在组织中分布良好，给药后第1天浓度达到最高。此时，肌肉、皮肤、肾脏、肝脏和鳃中MNZ的平均浓度分别为14999、20269、15070、10102和16467微克/千克。在整个停药期，所有鱼组织中MNZ均转化为MNZOH，MNZOH与MNZ的比例高达7%。这表明MNZ本身是虹鳟体内的主要残留物质。在肌肉、皮肤以及带皮肌肉中，MNZ在接近决策限（0.20微克/千克）水平下可检测到的时间长达42天，而在肾脏、肝脏和鳃中，给药后长达28天仍可检测到。MNZOH从鱼组织中消除得更快，仅在肌肉中存在长达21天。MNZ和MNZOH在虹鳟组织中的消除半衰期分别为1.83 - 2.53天和1.24 - 2.12天。当分析不带皮的肌肉时，检测到的MNZ和MNZOH浓度更高，且持续时间比带皮肌肉更长。因此，单独的肌肉可能更适合用于虹鳟体内MNZ有效残留量的控制。出于同样的原因，采样后立即确保直接冷却也至关重要，因为MNZ及其代谢产物在非冷冻条件下储存的鱼肌肉和皮肤中会降解。
