灰黄霉素在家兔组织中的分布及残留消除规律研究

Distribution and Residue Elimination of Griseofulvin in Rabbit Tissues

关键词:  灰黄霉素  家兔  组织分布  残留  LC-MS/MS

Key words:  Griseofulvin  Rabbit  Tissue distribution  Residue  LC-MS/MS

摘要:

摘要　目的：研究灰黄霉素在家兔组织中的分布及消除规律，为灰黄霉素用于治疗家兔真菌病的安全性评价提供依据。方法：选择42只新西兰白兔，于饲料中添加灰黄霉素（800g/1000 kg）混饲，连续饲喂14天，分别于停药后1、3、5、7、9、14、21d，各处死6只取其肝、肾、肌肉、皮肤及脑组织。以盐酸普萘洛尔为内标，使用二氯甲烷进行提取，用高效液相色谱—串联质谱仪（HPLC-MS/MS）进行各种组织中灰黄霉素浓度分析。结果：连续用药后，灰黄霉素在家兔组织中的分布情况为：肝组织浓度最高（134.61?g/kg），肾组织次之（54.09?g/kg)，脑组织浓度最低（未检出）；停药后，随着时间的延长，灰黄霉素在肌肉、肝、肾和皮肤组织中的浓度逐渐下降，且在肝脏中的消除速度最快，至停药21d，灰黄霉素在肾组织中浓度为3.39?g/kg，在肝组织中浓度为12.36?g/kg，其它组织低于定量限或未检出。结论：连续用药后，灰黄霉素在家兔肝、肾、肌肉和皮肤组织中均有分布，肝组织浓度最高；至停药21d，肝、肾组织中仍可检测到灰黄霉素残留。建议家兔生产中慎用灰黄霉素。

Abstract:

Abstract Objective: To study the distribution and elimination of griseofulvin in rabbit tissues, and to provide the basis for safety assessment of griseofulvin used for the treatment of rabbit fungal dermatopathy. Methods: Fourty-two rabbits were fed with pellet feed containing 800g/1000kg griseofulvin for 14 days.The liver, kidney muscle, skin and brain of 6 rabbits were collected at different time point (withdrawal days 1, 3, 5, 7, 9, 12 and 21). The concentrations of griseofulvin in rabbit tissues were determined by LC-MS/MS method. Results: After continuous treatment, the griseofulvin concentration in liver tissue was the highest (134.61μg/kg), followed by kidney tissue (54.09μg/kg), the concentration of griseofulvin in brain tissue was the lowest (not detetable). After treatment, griseofulvin in muscle, liver, kidney and skin tissues were gradually eliminated. To withdrawal day 21, the griseofulvin concentrations in liver and kidney tissue were respectively 12.36μg/kg and 3.39μg/kg. The griseofulvin concentrations in other tissues were below the detection limit of quantification or not detectable. The elelimination rate of griseofulvin in the liver tissue was found to be the rapiddest. Conclusions: After continuous treatment, griseofulvin are distributed in the rabbit liver, kidney, muscle and skin tissues, and the concentration in liver tissue is the highest. To withdrawal day 21, griseofulvin residues in liver and kidney tissue still can be detected. The results suggest that griseofulvin should be used with caution.