壳三糖在大鼠体内的组织分布和排泄研究  

Tissue distribution and excretion study of chitotriose in rats

作　　者：张朋朋 于明明[1,2] 吕志华 ZHANG Peng-peng;YU Ming-ming;LV Zhi-hua(Key Laboratory of Marine Drugs,Ministry of Education,Shandong Key Laboratory of Glycoscience and Glycotechnology,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Laboratory for Marine Drugs and Bioproducts of Qingdao Pilot National Laboratory for Marine Science and Technology,Qingdao 266237,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,山东省糖科学与糖工程重点实验室,医药学院,山东青岛266003 [2]青岛海洋科学与技术试点国家实验室海洋药物与生物制品实验室,山东青岛266237

出　　处：《中国海洋药物》2022年第4期73-79,共7页Chinese Journal of Marine Drugs

基　　金：山东省自然科学基金(ZR2019BC025)资助。

摘　　要：目的 研究壳三糖在大鼠体内的组织分布及排泄。方法 建立并验证了大鼠组织、尿液和粪便中壳三糖的高效液相色谱-质谱联用(LC-MS/MS)检测方法。大鼠灌胃给药壳三糖35 mg/kg后,分别在0.5、1.5、3.0 h摘取组织,0~4 h、4~8 h、8~12 h、12~24 h、24~36 h、36~48 h时间段收集尿液和粪便。用建立的LC-MS/MS方法测定组织、尿液和粪便中的壳三糖含量。结果 组织、尿液和粪便中壳三糖在10~10 000 ng/mL的浓度范围内线性良好,日内、日间精密度的相对标准偏差(relative standard deviation,RSD)≤14.20%,准确度的相对误差(relative error,RE)为-11.30%~8.33%,提取回收率为85.2%~97.9%,没有明显的基质效应,在室温放置24 h、反复冻融以及-40℃放置30 d的条件下稳定性良好,满足生物样品的检测需求。灌胃给药后,0.5 h就可以在主要组织检测到壳三糖,1.5 h肾脏中壳三糖含量明显升高,3 h未在大脑中检测到壳三糖。48 h后壳三糖在尿液、粪便中的排泄率分别为7.15%、72.80%。结论 壳三糖主要以原型的形式在大鼠体内分布和排泄,壳三糖在大鼠各组织中的分布较为广泛,以肝和肾为主,粪便是壳三糖的主要排泄途径。Objective To investigate the tissue distribution and excretion of chitotriose in rats. Methods A LCMS/MS method for the determination of chitotriose in tissues, urine and feces of rats was established and validated. Tissues were extracted at the time points of 0.5, 1.5 and 3.0 h and urine and feces were collected at 4, 8,12, 24, 36, 48 h after intragastrical administration at a dose of 35 mg/kg. The established LC-MS/MS method was used to determine the contents of chitotriose in tissues, urine and feces. Results The assay was linear over a concentration range of 10~10 000 ng/mL for chitotriose in tissues, urine and feces. The intra-day and interday precision of the investigated components exhibited an RSD within 14.20%, and the accuracy(RE) ranged from-11.30% to 8.33%. The extraction recovery of the chitotriose was determined between 85.2% and 97.9%.No significant matrix effects for chitotriose were observed. Chitotriose in tissues, urine and feces remained stable 24 h in room temperature, after freeze-thaw cycles, and 30 days in the-40 ℃ freezer. This method met the testing requirements of biological samples. Chitotriose could be determined in major tissues at 0.5 h, the content of chitotriose in kidney increased significantly at 1.5 h, and no chitotriose was discovered in brain at 3 h after intragastric administration. The excretion rates of chitotriose in urine and feces were 7.15% and 72.80% after 48 h, respectively. Conclusion Chitotriose was mainly distributed and excreted in the rat body in prototype form. Chitotriose was widely distributed in various tissues of rats, mainly in liver and kidney. Feces was the main excretion route of chitotriose.

关 键 词：壳三糖 高效液相色谱-质谱联用 组织分布 排泄 

分 类 号：R917[医药卫生—药物分析学]