High performance liquid chromatography-ion trap mass spectrometric analysis for metabolites of isoline in rat urine and bile
Author(s)
Author(s)
Zhang, F.
Zhong, D. F.
Wang, C.-H.
Wang, Z.
Date Issued
2008
Publisher
Informa
Journal
Drug Metabolism Reviews
Volume
40
Start page
141
End page
142
Abstract
Isoline is one major retronecine-type pyrrolizidine alkaloid from a Chinese medicinal herb (Ligularia duciformis) which has been used as an expectorant and anti-tussive agent in folk medicine. Many PAs including isoline are hepatotoxic, pheumotoxic, genotoxic, neurotoxic, which are responsible for toxication of both human being and livestock via consumption of PAs-containing plants. In the present study, we investigated the metabolites of isoline in urine and bile of rats following oral administration of 10mg/kg by combining high performance liquid chromatography and ion trap mass spectrometry (HPLC..Cion trap MS). Identification and structural elucidation of the metabolites were performed by comparing their changes in molecular ions ([M+ or -H]+or-], retention-times, and full scan MSn spectra with those of the parent compound. The results revealed that at least twenty four metabolites existed in rat urine and bile. The major route of metabolism in rats was hydrolysis, and the esterase(s) played a key role in the in vivo metabolism of isoline. The hydrolysis products, corresponding N-oxides and adducts conjugated with glycuronic acid, sulfation were shown to be the major metabolities in urine and bile, which might be a novel hydrolytic detoxication pathway for acetyl-containing PAs. Another route of metabolism was found that isoline could be translated to a set of dehydro-pyrrolizine derivatives in vivo, which commonly contained a highly reactive bifunctional electrophilic pyrroles and exerted toxicity.
SFU Affiliated Publication
No
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