A sensitive liquid chromatography-electrospray tandem mass spectrometric method for lancemaside A and its metabolites in plasma and a pharmacokinetic study in mice.
A high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method employing electrospray ionization (ESI) has been developed for simultaneous determination of lancemaside A (3-O-beta-D-glucuronopyranosyl-3beta, 16alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl ester) and its metabolites in mouse plasma. When lancemaside A (60 mg/kg) was orally administered to mice, echinocystic acid was detected in the blood. T(max) and C(max) of the echinocystic acid were 6.5+/-1.9 h and 56.7+/-29.1 ppb. Orally administered lancemaside A was metabolized to lancemaside X (3beta, 16alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl ester) by intestinal microflora in mice, which was metabolized to echinocystic acid by intestinal microflora and/or intestinal tissues. Human intestinal microflora also metabolized lancemaside A to echinocystic acid via lancemaside X. These results suggest that the metabolism by intestinal microflora may play an important role in pharmacological effects of orally administered lancemaside A.
Joh
Eun-Ha
EH
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, 1, Hoegi, Dongdaemun-Ku, Seoul 130-701, Republic of Korea.
Kim
Dong-Hyun
DH
D000818:Animals; D001419:Bacteria / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D008297:Male; D054892:Metagenome / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D015203:Reproducibility of Results; D012503:Saponins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
D012503:Saponins; C533150:lancemaside A; D009828:Oleanolic Acid; C022999:echinocystic acid