Chemical Analysis Of Dietary Supplements That Have Been Implicated In Hepatotoxicity

Herbal dietary supplements (HDS) are widely used, especially for weight loss. There is growing evidence to show that some HDS are capable of causing hepatotoxicity. The precise ingredient or combinations of ingredients responsible for injury, however, are difficult to determine given the multiplicity of compounds, the possibility of adulteration or contamination, and interaction of various compounds with one another. Chemical analysis using LC-QToF-MS was performed on known and suspected hepatotoxins from 35 dietary supplements that have been implicated in hepatotoxicity through the National Institutes of Health sponsored US Drug Induced Liver Injury Network; these suspected hepatotoxins include pyrrolizidine alkaloids (comfrey), EGCG (Green tea extract), amatoxins (mushrooms), aflatoxins, pharmaceuticals like NSAIDs, anabolic steroids. There are no spectral libraries for LC-MS identification. However, the molecular ion present in LC-MS analyses with its mass and elemental formula can be used to search a database of metabolites such as the Human Metabolome Database (www.hmdb.ca), Metlin Metabolite database (https://metlin.scripps.edu/index.php), ChemSpider (www.chemspider.com) or in-house developed database. In addition, the development of accurate mass time-of-flight mass spectrometers has enabled the calculation of an empirical formula from the molecular ion. Compound structures need to be confirmed with authentic standards, or further verified as far as possible by MS-MS fragmentation patterns together with any other structural information.

Acknowledgements: This research is supported in part by “Science Based Authentication of Dietary Supplements” funded by the Food and Drug Administration grant number 1U01FD004246 – 05. Supplements were obtained from a repository of products that have been implicated in liver injury.