title: The in vivo absorbed constituents and metabolites of Danshen decoction in rats identified by HPLC with electrospray ionization tandem ion trap and time-of-flight mass spectrometry.
abstract: Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge, is widely used for the treatment of cardiovascular and cerebrovascular diseases. This research focuses on the in vivo metabolism of Danshen decoction (DSD) in rats. After oral administration of DSD, the absorptive constituents and their metabolites in urine and plasma were analyzed by HPLC coupled with a photodiode array detector and electrospray ionization hybrid ion trap and time-of-flight mass spectrometry. Samples were separated on a C18 column by gradient elution using 0.1% (v/v) aqueous formic acid and acetonitrile. As a result, 93 compounds from urine and 38 compounds from plasma were identified. Among them, lipo-soluble diterpenoids (24 in urine and 15 in plasma) were reported for the first time as in vivo metabolites of DSD. According to the quantities and contents of the identified compounds, tanshinone IIA, cryptotanshinone and tanshinone I were deduced to be the major absorptive diterpenoids of DSD. Moreover, nine water-soluble phenolics (caffeic acid, ferulic acid, danshensu, etc.) were proved to be the major absorptive constituents as reported. Most of the absorbed constituents underwent sulfation, glucuronidation, hydrogenation and hydroxylation in vivo. This investigation provided scientific evidence to obtain a more comprehensive metabolic profile of DSD.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, The People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Shuai
authors.initials: S
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Guang-Xue
authors.initials: GX
authors.lastname: Liu
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Cai
mesh_terms: D045784:Abietanes / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D062385:Hydroxybenzoates / Q000032:analysis; D013058:Mass Spectrometry / Q000379:methods*; D010636:Phenols / Q000032:analysis; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D045784:Abietanes; D062385:Hydroxybenzoates; D010636:Phenols; C021751:tanshinone; C017616:phenolic acid
keywords: Danshen decoction; HPLC-DAD-ESI-IT-TOF/MS; metabolites in vivo; phenolic acid; tanshinone