Metabolic profiling of the flower of Citrus aurantium L. var. amara Engl. in rats using ultra‐high‐performance liquid chromatography coupled to quadrupole time‐of‐flight tandem mass spectrometry with data mining strategy

The flower of Citrus aurantium L. var. amara Engl. (FCAVA), an edible tea and herbal medicine with anti-obesity effect, has attracted great attention in China. The structural elucidation of chemical components in FCAVA has been realized in our previous work. It is well known that metabolic profiling provided a structural basis to discover potential anti-obesity ingredients in FCAVA. Nevertheless, there are no reports about in vivo metabolic profiles of FCAVA. Therefore, it is necessary to comprehensively identify in vivo substances of FCAVA.The identification of in vivo substances of FCAVA remains a challenge due to the strong interference of complex chemical components, biological matrices and metabolite isomers. In this work, ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) analysis with a data mining strategy was established and applied for the metabolic profiling of FCAVA in rats. The data mining strategy, including diagnostic product ions and neutral loss filtering, improved structural elucidation of xenobiotics in rats after oral administration of FCAVA.A total of 228 xenobiotics, including 80 prototypes (10 unambiguous confirmed with reference standards) and 148 metabolites, were tentatively characterized in rat plasma, urine and fecal samples. Among them, 35 xenobiotics were found in plasma, 124 in urine and 156 in feces. The main biotransformation pathway of FCAVA metabolism was deglycosylation, methylation, glucuronidation and sulfation. The main compounds absorbed into the blood were neohesperidin and naringin, which have been reported to show significant anti-obesity effect.Collectively, this present study would be conducive to the discovery of active ingredients of FCAVA for the treatment of obesity and the development of quality control of FCAVA.