【作者】 高杰；

【导师】 杨志强； 李建喜；

【作者基本信息】 甘肃农业大学 ， 临床兽医学， 2008， 硕士

【摘要】 喹胺醇是中国农业科学院兰州畜牧与兽药研究所研制的一种新型药物饲料添加剂,属于喹喔啉类不同侧链结构的衍生化合物,前期研究结果表明毒性和残留均低于同类药品。本实验利用平衡透析法对喹胺醇在鸡体内蛋白结合率研究,利用反相高效液相色谱法分析喹胺醇在鸡体内的主要排泄途径和标示残留代谢物,旨在对喹胺醇的用药及残留检测提供实验数据,进而为喹胺醇临床安全性全面评价提供科学依据。结果:(1)浓度为22.0、5.5、1.1μg/mL喹胺醇溶液,平衡透析时间为30±2 h,蛋白结合率分别为66.96±1.59%、75.30±1.92%、84.41±0.87%。(2)浓度为20.0、5.0、1.0μg/mL喹烯酮溶液,平衡透析时间为32±1 h,蛋白结合率分别为46.96±1.59%,55.30±1.92%,54.41±0.87%。(3)鸡口服喹胺醇200 mg/kg.B.W后,72 h内从粪中排泄原药的总量占总给药量的61%。(4)喹喔啉-2-羧酸可定为喹胺醇在鸡体内的一种标示残留物,其检测条件为:Agilent系列ZORBAX Eclipse XDB C18色谱柱(250 mm×4.6 mm,5μm),流动相为1%的甲酸水溶液:甲醇=(40:60),流速为1.0 mL/min,QCA的检测波长为320 nm。结论:(1)喹胺醇、喹烯酮的透析平衡时间均为30±3h,这与二者结构、分子质量相近有关;(2)喹胺醇与血浆蛋白结合有一定的饱和度,饱和后血浆蛋白的结合率与浓度间呈反比;(3)喹胺醇的血浆蛋白结合率比喹烯酮高;(4)喹胺醇在鸡体内的排泄主要由胃肠道直接排出体外;(5)喹喔啉-2-羧酸可以确定为喹胺醇在鸡体内的残留检测标示物。更多还原

【Abstract】 Kuianchun is a new drug of Quinoxlines developed by Lanzhou institute of animal sciences and veterinary pharmaceutics of Chinese academy of agricultural sciences. The previous studies showed that the toxicity and residue of Kuianchun were lower than those of olaquindox and others. In this study, the protein binding rate was evaluated by the equilibrium dialysis, the major excretion and the mark of residue were measured by RP-HPLC. The aims were to provide the data for clinic and residue detection and to provide evidences for evaluation of clinical safety on Kuianchun.RESULTS: (1) At concentration of 22.0μg/mL, 5.5μg/mL and 1.1μg/mL in buffer, the protein binding rates of Kuianchun were 66.96±1.59%, 75.30±1.92%, 84.41±0.87%respectively. The equilibrium dialysis time was 30±2h. (2) At concentration of 20.0μg/mL,5.0μg/mL and 1.0μg/mL in buffer, the protein binding rates of Quinocetone were 46.96±1.59%, 55.30±1.92%, 54.41±0.87% respectively. The equilibrium dialysis time was 30±1 h. (3) At the dose of 200 mg/kg.B.W, over 61% Kuianchun in chicken was excreted with the feces during 72 hours. (4) The Quinoxaline-2-Carboxylic acid was one of the marker residues of Kuianchun. Measured conditions of RP-HPLC to Quinoxaline-2-Carboxylic acid in chicken were ZORBAX Eclipse XDB C18 chromatographic column (250 mm×4.6 mm, 5μm), the mobile phase of 1 % formic acid–methyl alcohol (40/60, v/v), the flow rate of 1.0 mL·min-1, the UV detecting wavelength of 320 nm.CONCLUSION: (1) The equilibrium dialysis time was 30±3h both of Kuianchun and Quinocetone. There was a relationship among the equilibrium time and drug structure and molecular weight. (2) The protein combined with drug was terminated at the saturation. Then, the protein binding rate was decreased with increasing of drug concentration. (3) The protein binding rate of Quinocetone was lower than that of Kuianchun. (4) The much of Kuianchun in chicken was excreted with feces. (5) Quinoxaline-2-Carboxylic acid was one of the marker residues of Kuianchun.更多还原