文献类型：期刊文献

英文题名：Pharmacokinetics, bioavailability and tissue distribution of chitobiose and chitotriose in rats

作者：Chen, Mai[1];Jin, Jiayang[1];Ji, Xiaoguo[1];Chang, Kunlin[1];Li, Juan[2];Zhao, Liming[1,3]

机构：[1]East China Univ Sci & Technol, R&D Ctr Separat & Extract Technol Fermentat Ind, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Naval Med Univ, Chang Zheng Hosp, Dept Nutr, Shanghai 200003, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg Technol SC, Shanghai 200237, Peoples R China

年份：2022

卷号：9

期号：1

外文期刊名：BIORESOURCES AND BIOPROCESSING

收录：;EI(收录号：20224513080828);WOS:【SCI-EXPANDED(收录号:WOS:000754201500001)】；

基金：This research was financially supported by the National Key R&D Program of China (2019YFD0901805), the 111 Project (B18022) and the Fundamental Research Funds for the Central Universities, and the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, ECUST (ZDXM2019).

语种：英文

外文关键词：Chitobiose; Chitotriose; UPLC-MS; Pharmacokinetics; Tissue distribution

摘要：Chitooligosaccharides (COSs) have various physiological activities and broad application prospects; however, their pharmacokinetics and tissue distribution remain unclear. In this study, a sensitive and selective ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for determining chitobiose (COS 2) and chitotriose (COS 3) in rat serum and tissues was developed. This method was successfully validated based on FDA guidelines in terms of selectivity, calibration curves (lower limit of quantification was 0.002 mu g/mL for COS 2 and 0.02 mu g/mL for COS 3), precision (intra-day relative standard deviation of 0.04%-3.55% and inter-day relative standard deviation of 1.94%-11.63%), accuracy (intra-day relative error of - 1.81%-11.06% and inter-day relative error of - 9.41%-8.63%), matrix effects, recovery (97.10%-101.29%), stability, dilution integrity, and carry-over effects. Then, the method was successfully applied to the pharmacokinetics and tissue distribution study of COS 2 and COS 3 after intragastric and intravenous administration. After intragastric administration, COS 2 and COS 3 were rapidly absorbed, reached peak concentrations in the serum after approximately 0.45 h, and showed rapid elimination with clearances greater than 18.82 L/h/kg and half-lives lower than 6 h. The absolute oral bioavailability of COS 2 and COS 3 was 0.32%-0.52%. COS 2 and COS 3 were widely distributed in Wistar rat tissues and could penetrated the blood-brain barrier without tissue accumulation.