Analytical, pharmacokinetic and regulatory characterisation of selected plant N-alkylamides

Abstract

N-alkylamides (NAAs) are secondary metabolites occurring in many plants. These bioactive compounds, with many structural variations, are known to exert various pharmacological properties. This group of bioactive plant compounds was investigated in this doctoral research. Achillea millefolium and Achillea ptarmica are plants used in indigenous cultures to treat various stomach disorders. It was already demonstrated that some NAAs are responsible for the pharmacological properties. Therefore, the NAAs were analytically characterised in both plant extracts using two different analytical techniques (HPLC-ESI-MS and GC-EI-MS). Furthermore, the transdermal and intestinal properties of the plant NAAs pellitorine and spilanthol were evaluated. In this research, these NAAs were topically applied on human skin and orally given to rats to investigate if these NAAs were able to reach the blood circulation. Once in the blood circulation, the blood-brain barrier permeability properties were quantitatively evaluated. The use of a single quadrupole MS detector was shown in high-throughput transdermal research. The advantages of this type of detector were demonstrated, compared to an ultraviolet detector, e.g. a gain in selectivity and lower limit of detections were obtained. Lastly, the regulatory status of N-alkylamide containing health products was discussed. Products containing NAAs are widely available on the market as e.g. food supplements, medicinal products, cosmetics and medical devices. Currently, no unambiguous legal product classification for these products exist. The classification is dependent on the dose of the bioactive NAAs, their (claimed) use and their biological functionalities