Profiling the metabolic difference of seven tanshinones using high‐performance liquid chromatography/multi‐stage mass spectrometry with data‐dependent acquisition

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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. Copyright © 2007 John Wiley & Sons, Ltd.

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