硫酸阿米卡星在鳗鲡体内的药动学和残留研究论文.pdfVIP

硫酸阿米卡星在鳗鲡体内的药动学和残留研究 尹文林 ，沈锦玉，何 平，徐 洋，姚嘉 赟 (浙江省淡水水产研究所，浙江湖州 313000) 摘要: 组织用高氯酸提取、固相萃取净化，2,4,6-三硝基苯磺酸、吡啶、4-二甲基氨基吡啶、三氟乙酸柱前衍生后， 高效液相紫外检测法测定了硫酸阿米卡星在鳗鲡体内药代动力学和残留。流动相为 45% 0.02M 磷酸二氢钾：41% 乙腈：14% 甲醇，50% 氢氧化钾溶液调节 pH 为 7.7 ；流速：1.5 ml/min；检测波长为340nm 。该方法的衍生产物 稳定，0.05-100μg/ml 浓度范围内线性关系良好（R=0.9995 ），最低检测限为 0.1μg/ml(μg/g) 。血液和肌肉中的平均 回收率分别为 75.9±2.9%和 76.9±4.6% 。鳗鲡在(26±1)℃时，以 50mg/kg 单剂量肌肉注射给药物后，鳗鲡血液中的 药－时浓度符合一级吸收二室模型，其主要的药动学参数为：达峰时间(Tpeak)0.597h，分布半衰期(T1/2α) 3.52h， 表明硫酸阿米卡星在鳗鲡体内吸收分布迅速。峰浓度(Cmax)为 22.229μg/ml，消除半衰期(T1/2β)为 46.945h ，推测 该药物可能残留时间比较长。鳗鲡在 26±1 ℃时，50mg/kg 单剂量肌肉注射硫酸阿米卡星后，5d 后在肌肉组织中 未检出，19d 后血液中未检出。 关键词：硫酸阿米卡星；鳗鲡；药物代谢动力学；残留；柱前衍生固相萃取 The Studies on Pharmacokinetics of Amikacin Sulfate in Anguilla Japonica YIN Wenlin, SHEN Jinyu, HE Ping, XU Yang, YAO Jiayun (Zhejiang institute of freshwater fisheries, Huzhou 313000, Zhejiang, China) Abstract: A high performance liquid method is described for determination of amikacin sulfate in the tissue of Anguilla japonica. Amikacin sulfate was extracted from samples with Perchloric acid and purified by using solid-phase extraction. The drug was derivatized by 2,4,6-trinitro-benzenesulfonic acid(TNBS), pyridine, 4-dimethylaminopyridine and triflouroacetic. The derivatization was analyzed by HPLC with a Agilent XDB-C18 column (5μm ，4.6mm×250mm). The mobile phase was a mixture of 45% potassium phosphatemonobasic(0.02M), 41% acetonitrile, 14% methanol( adjusted for a final pH of 7.7 with 50% sodium hydroxide) ,at a flow rate of 1.5ml/min and the UV-detector was set as 340nm.. The drug concentrations in Anguilla japonica tissue were determined by the above method. The obtained data were analyzed