| 摘要: |
| 【目的】研究三氮脒在羊体内的消除规律，为保障动物源食品安全提供理论依据。【方法】分别配制质量浓度为0.05，0.1，0.2，0.5，1，2和5 μg/mL的三氮脒标准液，进行高效液相色谱分析，建立三氮脒标准曲线。采集空白羊肌肉、肝脏、肾脏的组织样品，进行三氮脒加标试验，测定批内平均回收率和批内、批间相对标准偏差，建立羊组织中三氮脒残留的高效液相色谱检测方法。选取35只健康湖羊，逐只按5 mg/kg的剂量颈部肌内注射三氮脒3次，每次间隔24 h，在最后一次给药后0.25(6 h)，1，3，7，14，21，28 d，分别采集肌肉、肝脏、肾脏和注射部位等组织，采用高效液相色谱法测定各组织中三氮脒的残留量，并用WinNonlin5.2.1软件计算药物消除动力学参数。【结果】在质量浓度为0.05～5 μg/mL时，三氮脒质量浓度与峰面积线性关系良好，相关系数（r）为0.999 5；三氮脒高效液相色谱法对羊肌肉的检测限为50 μg/kg，定量限为100 μg/kg；对羊肝脏、肾脏的检测限为200 μg/kg，定量限为500 μg/kg；批内平均回收率为83.1%～94.8%，批内相对标准偏差为2.6%～6.2%，批间相对标准偏差为3.0%～4.9%。在给药后6 h，供试湖羊肌肉、肝脏、肾脏和注射部位三氮脒残留量达到最高值，随后在各个检测时点各组织残留量均呈下降趋势；在给药后21 d，肌肉组织中未检出三氮脒残留，肾脏组织和注射部位（定量限同肌肉）中三氮脒的平均残留量降至定量限以下，肝脏中三氮脒的平均残留量也明显降低；给药后28 d，羊各组织均未检出三氮脒残留。三氮脒在羊肌肉、注射部位、肾脏和肝脏组织中的消除半衰期（T1/2β）分别为104.21，99.55，102.66和149.42 h，药时曲线下面积（AUC）分别为113.20，349.33，3 658.62和3 370.83 （h·μg）/g，消除速率（β）分别为0.006 6，0.007 0，0.006 7和0.004 6 h－1，平均滞留时间（MRT）分别为125.11，140.62，71.20和154.71 h。【结论】三氮脒经肌内注射给药后，在羊体内分布广泛、消除缓慢，在肝脏和肾脏组织中残留量较高。 |
| 关键词: 三氮脒 羊组织 药物残留 药物消除 |
| DOI： |
| 分类号: |
| 基金项目:国家畜禽产品质量安全风险评估专项（GJFP2018007） |
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| Elimination of diminazene residue in sheep |
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JIANG Di,WU Zhiming,WU Ningpeng,et al
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| Abstract: |
| 【Objective】The elimination of diminazene residue in sheep was investigated to provide basis for safety of animal-derived food.【Method】The diminazene standard solution with mass concentrations of 0.05，0.1，0.2，0.5，1,2 and 5 μg/mL was prepared separately to establish a standard curve of diminazene.Then muscle,liver and kidney samples of blank sheep were collected for performing spiked test and determining average recovery in the batch as well as intra-day RSD and inter-day RSD.Then,the high-performance liquid chromatography was established for the diminazene residue in sheep tissues.A total of 35 healthy Hu sheep were selected and intramuscularly injected with diminazene at the dosage of 5 mg/kg every 24 h for 3 times.Muscle,liver,kidney and inject site samples were collected 0.25(6 h),1，3，7，14，21 and 28 d after the last injection.Diminazene residue in these samples were analyzed by HPLC-UV and pharmacokinetic parameters were estimated using WinNonlin 5.2.1 software.【Result】In the range of 0.05-5 μg/mL,diminazene residue and peak area had good linearity with r of 0.999 5.The detection limit for muscle was 50 μg/kg,and the quantitation limit was 100 μg/kg.The detection limit for liver and kidney was 200 μg/mL,and the quantitation limit was 500 μg/mL.The recoveries ranged from 83.1%-94.8%.The intra-day relative standard deviation was 2.6%-6.2% and the inter-day relative standard deviation was 3.0%-4.9%.The concentration of diminazene residue in muscle,liver,kidney and inject site at 6 h was the highest,and the concentration of dimimzaene in all tissues decreased at other time points.The concentration of diminazene in muscle was lower than the LOQ at 21 d,and the average residue of dimimzaene in kidney and injection site (the quantification limit at injection site was same as that of muscle) fell below the quantitation limit.The average residue of dimimzaene in liver was also significantly reduced,and the residue in all tissues was not detected at 28 d.The elimination half-life (T1/2β) values of diminazene in muscle,inject site,kidney and liver were 104.21，99.55，102.66 and 149.42 h,respectively.The areas under concentration time curve (AUC) were 113.20，349.33，3 658.62 and 3 370.83 (h·μg)/g,respectively.The elimination rates (β) were 0.006 6，0.007 0，0.006 7 and 0.004 6 h－1 and the mean residence times (MRT) were 125.11，140.62，71.20 and 154.71 h,respectively.【Conclusion】The results demonstrated that diminazene distributed widely and metabolized slowly in sheep.The concentration of diminazene residue was high in liver and kidney tissue. |
| Key words: diminazene sheep tissues drug residue drug depletion |
