title: Safety assessment of food and herbal products containing hepatotoxic pyrrolizidine alkaloids: interlaboratory consistency and the importance of N-oxide determination.
abstract: BACKGROUND
  Two recent mass spectrometry-based reports concerning Senecio scandens yielded remarkably dissimilar pyrrolizidine alkaloid constituents. In both studies, and in a related analysis of Senecio scandens and Tussilago farfara using micellar electrokinetic chromatography, the presence of hazardous N-oxides of the alkaloids was either not considered or was inadequately considered. This raises concerns about the effectiveness of the methodologies used in these, and similar, studies in assessing the pyrrolizidine alkaloid content and the safety of food, food supplements and medicines for human use.
  
  
  OBJECTIVE
  To highlight essential analytical requirements for confident assessment of pyrrolizidine alkaloid-related safety of food and herbal products for human use.
  
  
  METHODS
  Direct infusion-ESI MS and HPLC-ESI MS were used to analyse samples derived from liquid-liquid partitioning experiments and from strong cation exchange, solid-phase extraction of pyrrolizidine alkaloids and their N-oxides.
  
  
  RESULTS
  A simple solvent partitioning experiment using pure senecionine and senecionine-N-oxide, two constituents reported in one of the mass spectrometry-based studies of S. scandens, clearly demonstrated the inadequacy of the reported method to detect and quantitate hazardous pyrrolizidine alkaloid N-oxide components. A preliminary LCMS analysis of commercially-prepared extracts of comfrey roots (Symphytum officinale and S. uplandicum s. l.) was used as a model to highlight the analytical importance of N-oxides in the safety assessment of pyrrolizidine alkaloid-containing medicinal herbs.
  
  
  CONCLUSIONS
  This study highlighted significant differences in the reported identification of pyrrolizidine alkaloids from the same plant species, and clearly demonstrated the inadequacy of some procedures to include N-oxides in the assessment of pyrrolizidine alkaloid-related safety of food and herbal products.
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Plant Toxins Research Group, Private Bag 24, Geelong, Victoria 3220, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Steven M
authors.initials: SM
authors.lastname: Colegate
authors.forename: John A
authors.initials: JA
authors.lastname: Edgar
mesh_terms: D002851:Chromatography, High Pressure Liquid; D020844:Comfrey / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000032:analysis*; D005504:Food Analysis / Q000379:methods*; D006801:Humans; D010946:Plants, Medicinal / Q000737:chemistry*; D011763:Pyrrolizidine Alkaloids / Q000032:analysis*; D012674:Senecio / Q000737:chemistry; D052616:Solid Phase Extraction / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D003497:Cyclic N-Oxides; D011763:Pyrrolizidine Alkaloids