Structural elucidation of in vitro and in vivo metabolites of cryptotanshinone by HPLC–DAD–ESI–MSn

The structural elucidation of the in vivo and in vitro metabolites of cryptotanshinone which was the major active component isolated from rhizome of Salvia miltiorrhiza Bunge and possessed significant antibacterial, anti-dermatophytic, antioxidant, anti-inflammatory and anticancer activities was described. Nineteen phase I metabolites and six phase II metabolites of cryptotanshinone were elucidated and identified by a sensitive LC–DAD–ESI–MSn method, and their molecular structures were proposed on the basis of the characteristics of their precursor ions, product ions, chromatographic retention time and ultraviolet spectra. The in vivo and in vitro phase I metabolites were mainly biotransformed by four main routes, which were dehydrogenation, hydroxylation, furan ring cleavage and oxidation metabolism, and among these phase I reactions, dehydrogenation was the predominant metabolic pathway. Six in vivo phase II metabolites were identified as the glucuronided and the sulfated conjugates which showed a neutral loss of 176 and 80 Da, respectively. The biotransformation pathways of cryptotanshinone were proposed on the basis of this research.