Dehydropyrrolizidine Alkaloids in Boneset (Eupatorium perfoliatum L.) and Three Related Species

Dehydropyrrolizidine alkaloids (DHPA) have been associated with hepatic veno-occlusive disease. In addition to acute hepatotoxicity, long-term, low-level, or intermittent exposures may contribute to chronic diseases. Eupatorium perfoliatum is a medicinal herb referred to as 'boneset'. The presence of DHPA has been reliably reported in some Eupatorium species, but reports on E. perfoliatum have been contradictory. Although not a big seller in mass markets, boneset is used by medical herbalists in the U.S. A number of boneset samples were acquired for analysis. The herb, alcoholic tinctures, hot water infusions, and decoctions made from a subset of those samples were analyzed. Eupatorium perfoliatum and three closely-related species were subjected to extraction and HPLC-esi(+)MS and MS/MS. Dehydropyrrolizidine alkaloids were identified from their MS data and comparison with standards. Forty collections of E. perfoliatum were tested and shown to contain DHPA, dominated by lycopsamine and intermedine, their N-oxides and acetylated derivatives. Concentrations varied from 0.0002 – 0.07% (w/w). Alcoholic tinctures, hot water infusions, and decoctions also had high concentrations of the alkaloids. Contamination of some E. perfoliatum samples with related species was suggested by the co-presence of retronecine- and heliotridine-based dehydropyrrolizidine alkaloids. It is unknown whether sampling issues, the existence of low and high alkaloid chemotypes, or hybridization contribute to the wide variation in dehydropyrrolizidine alkaloid content observed. Nonetheless, this study definitively demonstrates that E. perfoliatum contains DHPA and provides a reason for caution until further research can better define the toxicity and carcinogenicity of the DHPAs of boneset.