Short communicationA sensitive liquid chromatography–electrospray tandem mass spectrometric method for lancemaside A and its metabolites in plasma and a pharmacokinetic study in mice
Introduction
Lancemaside A, 3-O-β-d-glucuronopyranosyl-3β, 16α-dihydroxyolean-12-en-28-oic acid 28-O-β-d-xylopyranosyl(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl ester, is a triterpenoid saponin isolated from BuOH extract of the rhizome of Codonopsis lanceolata (family Campanulaceae) [1]. Triterpenoid saponins of the rhizome of C. lanceolata, which contain lancemaside A as a major compound, are identified by centrifugal partition chromatography and liquid chromatography–mass spectrometry [2], [3], [4]. The rhizome of C. lanceolata is been used in herbal medicines for inflammatory diseases such as bronchitis and cough in Asian countries [5], [6], [7]. Their saponins exhibit anti-inflammatory and anti-tumor effects [7], [8]. We also reported that lancemaside A isolated from its BuOH fraction potently inhibited colitis via TLR-linked NF-κB activation in mice [9]. Similar to other saponins, such as ginsenoside Rb1, the absorption of orally administered lancemaside A from intestine into the blood may be difficult due to its hydrophilicity [10], [11], [12], [13]. Thus, orally administered lancemaside A comes into contact with intestinal microflora in intestine and is metabolized to hydrophobic compounds and its metabolites may be absorbed into the blood.
Therefore, to understand its bioactive form, we performed a pharmacokinetic study of lancemaside A in mice.
Section snippets
Chemicals, materials and reagents
Lancemaside A was isolated from C. lanceolata (CL) as previously reported by Joh et al. [9]. Compound K was isolated using the previously published method of Bae et al. [14]. β-d-Glucuronidase was purchased from Sigma (St Louis, MO, USA). Acetonitrile, methanol and formic acid (HPLC grade) were purchased from Samchun Chemicals (Pyeongtaek, Gyeonggi, Korea). All other reagents were of analytical grade.
Animals
Male ICR mice (24–28 g) were supplied from Orient animal breeding center (Seoul, Korea). All
Method validation
Lancemaside A, lancemaside X and echinocystic acid 3-O-β-d-glucuronopyranoside gave a fairly strong mass response in positive ESI mode, while echinocystic acid gave a fairly strong mass response in negative ESI mode. The ion peaks of lancemaside A and its metabolites were difficult to find. Overall, lancemaside A, lancemaside X, EAG and echinocystic acid gave a strong mass response in negative electrospray ionization (ESI) mode. By negative ESI, lancemaside A, lancemaside X, EAG, echinocystic
Conclusion
In this study, we developed a rapid, sensitive and selective LC–MS/MS method and validated its use for the determination of lancemaside A, lancemaside X, EAG, and echinocystic acid in mouse plasma. When lancemaside A (60 mg/kg) was orally administered to mice, echinocystic acid was detected in the blood, but lancemaside A, lancemaside X and EAG were not detected. Tmax and Cmax of echinocystic acid were 6.5 ± 1.9 h and 56.7 ± 29.1 ppb, respectively. Orally administered lancemaside A was metabolized to
Acknowledgement
This research was supported by a grant (09172 KFDA 996) from Korean Food and Drug Administration in 2009.
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