USP adopts new Chapter on Pyrrolizidine Alkaloids

The USP adopted the new general chapter <1567> Pyrrolizidine Alkaloids as Contaminants. The chapter was previously published for comments in Pharmacopeial Forum PF 48(1). The final version has been published in USP-NF 2023 Issue 3 (to be official on 1 December 2023).

Background

Pyrrolizidine Alkaloids (PAs) are naturally occurring heterocyclic phytotoxins that have been reported to be hepatotoxic, mutagenic, and carcinogenic. USP's new informational general chapter <1567> is intended to provide an overview of PAs which can contaminate or be present in many plant-related products (e.g. honey). Due to the presence of PA-containing plants growing near plants of interest and being accidentally coharvested, PAs can be found as contaminants in herbal medicinal products (HMPs). However, published literature reports suggest that tea and herbal infusions were the main contributors to total PA exposure. Therefore, "efforts should be made to obtain information specifically on the sources of PA contamination in tea, such as the adventitious PA-containing plants responsible for the contamination, and to use measures to control infestation and coharvest".

28 PAs recommended to be monitored

Twenty-eight PAs are selected to be monitored. Manufacturers of HMPs should evaluate the levels of PAs in their product considering their potential presence arising from the plant itself, from contamination with external PAs (e.g., due to coharvesting, absorbed from soil), and/or from supply chain vulnerabilities. In addition, they should use a risk-based approach for determining appropriate limits and testing requirements. The range of tolerable daily intake levels is provided in a table summarizing existing regulations governing PA-levels in food and food supplements that have been established in several countries (e.g. USA, Germany, Netherlands).

Regarding analytical methods it is mentioned that "extraction and analytical quantitation of PAs is associated with several challenges and would benefit from evolving strategies for both efficient extraction and advanced selective analytical quantification techniques. Future developments will hopefully lead to a greater availability of reference standards and method validation as regulatory bodies create requirements for accurate quantitation of PAs".

More information is available in the USP-NF.