title: Profiling the metabolic difference of seven tanshinones using high-performance liquid chromatography/multi-stage mass spectrometry with data-dependent acquisition.
abstract: Tanshinones are a class of bioactive constituents in the roots of Salvia miltiorrhiza named Dan-Shen in Chinese, which possess diverse pharmacological activities. In this study, we employed a sensitive high-performance liquid chromatography/multi-stage mass spectrometry (HPLC/MS(n)) method with data-dependent acquisition and a dynamic exclusion program for the identification of phase I metabolites of seven tanshinones in rat bile after intravenous administration. These seven tanshinones are tanshinone IIA, sodium tanshinone IIA sulfonate (abbreviated as STS, a water-soluble derivate of tanshinone IIA), cryptotanshinone, 15,16-dihydrotanshinone I, tanshinone IIB, przewaquinone A and tanshinone I. Altogether 33 metabolites underwent monohydroxylation, dihydroxylation, dehydrogenation, D-ring hydrolysis or oxidation reactions in the C-4 or C-15 side chain which were characterized by analyzing the LC/MS(n) data. Different metabolic reactions for tanshinones were dependent on the degree of saturation and the substituent group in the skeleton. Dehydrogenation was the major metabolic modification for cryptotanshinone with saturated A and D rings. 15,16-Dihydrotanshinone I containing a saturated D ring was mainly metabolized through D-ring hydrolysis. For tanshinone IIA, possessing a saturated A ring, hydroxylation was the major metabolic pathway. When there was hydroxyl group substitution in the C-17 or C-18 position, such as przewaquinone A and tanshinone IIB, or sulfonic group substitution in the C-16 position, such as STS, higher metabolic stability than that of tanshinone IIA was shown and only trace metabolites were generated. Oxidation in the C-4 or C-15 side chain was a characteristic reaction for tanshinone IIA and hydroxylated tanshinone IIA. For tanshinone I, bearing unsaturated A and D rings simultaneously, no metabolites were detected.
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, P. R. China.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.forename: Baorong
authors.initials: B
authors.lastname: Wang
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Ma
authors.forename: Man
authors.initials: M
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Dean
authors.initials: D
authors.lastname: Guo
mesh_terms: D045784:Abietanes; D000818:Animals; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016247:Information Storage and Retrieval / Q000379:methods; D007275:Injections, Intravenous; D013058:Mass Spectrometry / Q000379:methods*; D008657:Metabolic Clearance Rate; D010616:Phenanthrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D045784:Abietanes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; C021751:tanshinone