Profiling and identification of the metabolites of baicalin and study on their tissue distribution in rats by ultra-high-performance liquid chromatography with linear ion trap-Orbitrap mass spectrometer

摘要

Baicalin (baicalein 7-O-glucuronide), which is one of the major bioactive constituents isolated from Scutellariae Radix, possesses many biological activities, such as antiallergic, antioxidation, and anti-inflammatory activities. In the present study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of baicalin in rat plasma, urine, and various tissues. A combination of post-acquisition mining methods including extracted ion chromatogram (EIC) and multiple mass defect filters (MMDF) was adopted to identify the common and uncommon baicalin metabolites from the full mass scan data sets. Their structures were elucidated based on the accurate mass measurement, relevant drug biotransformation knowledge, the characteristic collision induced fragmentation pattern of baicalin metabolites, and bibliography data. Based on the proposed strategy, a total of 32 metabolites were observed and characterized. The corresponding reactions in vivo such as methylation, hydrolysis, hydroxylation, methoxylation, glucuronide conjugation, sulfate conjugation, and their composite reactions, were all discovered in the study. The results demonstrated that the rat liver and kidney are the most important organs for the baicalin metabolites presence. Six metabolites might play an important role in exerting pharmacological effects of baicalin in vivo. The newly discovered baicalin metabolites significantly expanded our understanding on its pharmacological effects, and could be targets for future studies on the important chemical constituents from herbal medicines. (C) 2015 Published by Elsevier B.V.