Pharmacokinetics and metabolism of lithospermic acid by LC/MS/MS in rats.
The pharmacokinetics and metabolism of lithospermic acid (LA), a component isolated from Salvia miltiorrhiza, and its two O-methylated metabolites (3'-monomethyl- and 3',3''-dimethyl-lithospermic acid), were analyzed by a rapid and specific isocratic liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Rat serum samples collected after intravenous and oral administration were analyzed for obtaining pharmacokinetic data of LA. Two O-methylated metabolites, namely one 3'-monomethyl- and one 3',3''-dimethyl-lithospermic acid were detected in rat serum and bile samples after intravenous and oral administration of LA, respectively. An oral bioavailability of 1.15% was found, with the AUC(0-t) values of 301.89 and 3.46mgh/L for intravenous and oral administration, respectively. The total recovery from bile was 75.36% (0.46% for LA, 17.23% for M1, and 57.67% for M2) after intravenous administration, and 4.26% (0.00% for LA, 0.10% for M1, and 4.16% for M2) after oral administration. These results indicate that methylation is the main metabolic pathway of LA, and that LA is excreted into rat bile and finally into feces.
Wang
Li
L
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Qiang
Q
Li
Xiaochuan
X
Lu
Youli
Y
Xue
Zhimou
Z
Xuan
Lijiang
L
Wang
Yiping
Y
D000818:Animals; D001572:Benzofurans / Q000378:metabolism* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D053630:Depsides / Q000378:metabolism* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D051381:Rats
D001572:Benzofurans; D053630:Depsides; C046833:lithospermic acid