Pharmacokinetics, bioavailability and tissue distribution of chitobiose and chitotriose in rats.

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 µg/mL for COS 2 and 0.02 µg/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. Highlights: Report of tissue distribution of chitobiose and chitotriose after intragastric administration in rats. A trace detection method for the determination of chitobiose and chitotriose in rat serum and organs using UPLC–MS was developed and validated. Our results reveal that chitobiose and chitotriose could be quickly absorbed into the blood, with an oral bioavailability of 0.32%–0.52% in rats. [ABSTRACT FROM AUTHOR]