Study of tanshinone IIA tissue distribution in rat by liquid chromatography‐tandem mass spectrometry method

Abstract

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for determining tanshinone IIA in rat tissues. After a single step liquid-liquid extraction with diethyl ether, tanshinone IIA and loratadine (internal standard) was subjected to LC/MS/MS analysis using positive electro-spray ionization under selected reaction monitoring mode. Chromatographic separation of tanshinone IIA and loratadine was achieved on a Hypersil BDS C(18) column (i.d. 2.1 x 50 mm, 5 microm) with a mobile phase consisting of methanol-1% formic acid (90:10, v/v) at a flow rate of 300 microL/min. The intra-day and inter-day precision of the method were less than 10.2 and 12.4%, respectively. The intra-day and inter-day accuracies ranged from 99.7 to 109.7%. The lowest limit of quantification for tanshinone IIA was 1 ng/mL. The method was applied to a tanshinone IIA tissue distribution study after an oral dose of 60 mg/kg to rats. Tanshinone IIA tissue concentrations decreased in the order of stomach > small intestine > lung > liver > fat > muscle > kidneys > spleen > heart > plasma > brain > testes. Tanshinone IIA still could be detected in most of the tissues at 20 h post-dosing. These results indicate that the LC/MS/MS method was rapid and sensitive to quantify tanshinone IIA in different rat tissues.

Pharmacokinetic characterization of hydroxylpropyl-β-cyclodextrin-included complex of cryptotanshinone, an investigational cardiovascular drug purified from Danshen (Salvia miltiorrhiza)

“…In the oral administration study, extensive accumulation of CTS and TS was observed in the stomach, intestine, lung and liver. These results are similar to that of TS (Bi et al 2007). For intravenous administration, the lung, followed by the liver, had the highest accumulation of CTS.…”

Disposition Pathways and Pharmacokinetics of Herbal Medicines in Humans

“…Tanshinone IIA was highly bound to plasma proteins (99.2 %), with lipoprotein being the major binder (77.5 %) [85]. In another study in rats, tanshinone IIA was found to be extensively distributed to the stomach and small intestines (1,800-and 37-fold of the level in plasma, respectively), with the lowest distribution to the brain and testis [86]. This suggests the substantial role of blood-brain (BBB) and blood-testis barriers in limiting the brain and testis penetration of tanshinone IIA.…”

Simultaneous determination of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone in rat plasma by liquid chromatography–tandem mass spectrometry: application to a pharmacokinetic study of a standardized fraction of Salvia miltiorrhiza, PF2401‐SF

“…1) Yang et al, 2006;Zhou et al, 2006;Ma et al, 2007). These tanshinones possess a variety of biological activities including antioxidative, antiinflammatory, antitumor, antifibrotic, antiischemic and antiapoptotic activities (Sung et al, 1999;Ng et al, 2000;Kim et al, 2002Kim et al, , 2003Wang et al, 2005;Bai et al, 2007;Chen et al, 2007;Park et al, 2007).…”

“…Dihydrotanshinone I was metabolized to tanshinone I by dehydrogenation, hydroxyl-dihydrotanshinone I by hydroxylation, and danshenxinkun A and tanshinone VI by D-ring hydrolysis in rats (Sun et al, 2007a). The pharmacokinetics of cryptotanshinone and tanshinone IIA were evaluated by LC-MS or LC-MS/MS methods after administration of cryptotanshinone, tanshinone IIA or various Danshen formulations to rats, rabbits or pigs (Li et al, 2005(Li et al, , 2006aSong et al, 2005;Zhou et al, 2005;Hao et al, 2006a,b;Bi et al, 2007). Neither the analytical methods for simultaneous determination of dihydrotanshinone I and tanshinone I in rat plasma nor the pharmacokinetics data of dihydrotanshinone I and tanshinone I have been reported.…”