Core Imprinting: An Alternative and Economic Approach for Depleting Pyrrolizidine Alkaloids in Herbal Extracts

Abstract

Due to the high toxicity of pyrrolizidine alkaloids, in 2011, the German Federal Institute of Risk Assessment recommended that their daily intake limit should be no more than 0.007 µg/kg body weight. The risk of ingesting these substances in herbal preparations, either from their inherent presence in plants or through contamination with pyrrolizidine alkaloid-containing weeds, should not be underestimated. A promising molecular imprinted polymer was developed previously to minimise exposure to these compounds. Due to the high costs of the template and the risk of template bleeding, an alternative and more economic pyrrolizidine alkaloid depleting strategy is still required. Core imprinting, which focuses on the most important structural element in the target molecule, was investigated using triethylamine and tetraethylammonium as easily available and cheap alternative templates. The suitability of core imprinting was demonstrated using a pyrrolizidine alkaloid standard solution if an excess of an alternative template compared to monocrotaline was used for imprinting. Matrix trials in pyrrolizidine alkaloid-spiked Mentha piperita, Chelidonium majus, Glycyrrhiza glabra, and Matricaria chamomilla extracts containing Echium vulgare revealed better pyrrolizidine alkaloid binding than demonstrated for the original molecular imprinted polymer. Echimidine and echimidine-N-oxide were depleted in the range of 31.8–70.0 and 26.1–45.1%, respectively. However, solvent-dependent differences in pyrrolizidine alkaloid binding and inherent plant analytical marker compounds were observed. Hence, binding of analytical marker compounds was better minimised in methanolic than in ethanolic extracts. The present study reveals core imprinting to be an economic alternative approach for depleting pyrrolizidine alkaloids in plant extracts.

Key words

Pyrrolizidine alkaloids - core imprinting - Mentha piperita - Matricaria chamomilla - Chelidonium majus - Glycyrrhiza glabra

• References

• 1 Roeder E.. Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie 1995; 50: 83-98
• 2 Analytik und Toxizität von Pyrrolizidinalkaloiden sowie eine Einschätzung des gesundheitlichen Risikos durch deren Vorkommen in Honig. Available at: https://www.bfr.bund.de/cm/343/analytik-und-toxizitaet-von-pyrrolizidinalkaloiden.pdf, Accessed January 7, 2019
• 3 Colegate SM, Gardner DR, Betz JM, Fischer OW, Liede-Schumann S, Boppré M.. Pro-toxic 1,2-Dehydropyrrolizidine Alkaloid Esters, Including Unprecedented 10-Membered Macrocyclic Diesters, in the Medicinally-used Alafia cf. caudata and Amphineurion marginatum (Apocynaceae: Apocynoideae: Nerieae and Apocyneae). Phytochem Anal 2016; 27: 257-276
• 4 Hartmann T.. Chemical ecology of pyrrolizidine alkaloids. Planta 1999; 207: 483-495
• 5 Mattocks AR.. Toxicity of pyrrolizidine alkaloids. Nature 1968; 217: 723-728
• 6 Bush LP, Fannin FF, Siegel MR, Dahlman DL, Burton HR.. Chemistry, occurrence and biological effects of saturated pyrrolizidine alkaloids associated with endophyte-grass interactions. Agric Ecosyst Environ 1993; 44: 81-102
• 7 Andersson LI, Paprica A, Arvidsson T.. A highly selective solid phase extraction sorbent for pre- concentration of sameridine made by molecular imprinting. Chromatographia 1997; 42: 57-62
• 8 Theodoridis G, Manesiotis P.. Selective solid-phase extraction sorbent for caffeine made by molecular imprinting. J Chromatogr A 2002; 948: 163-169
• 9 Ferrer I, Lanza F, Tolokan A, Horvath V, Sellergren B, Horvai G, Barceló D.. Selective trace enrichment of chlorotriazine pesticides from natural waters and sediment samples using terbuthylazine molecularly imprinted polymers. Anal Chem 2000; 72: 3934-3941
• 10 Chapuis F, Pichon V, Lanza F, Sellergren S, Hennion MC.. Optimization of the class-selective extraction of triazines from aqueous samples using a molecularly imprinted polymer by a comprehensive approach of the retention mechanism. J Chromatogr A 2003; 999: 23-33
• 11 Cacho C, Turiel E, Martin-Esteban A, Pérez-Conde C, Cámara C.. Characterisation and quality assessment of binding sites on a propazine-imprinted polymer prepared by precipitation polymerisation. J Chromatogr B Anal Technol Biomed Life Sci 2004; 802: 347-353
• 12 Maier NM, Buttinger G, Welhartizki S, Gavioli E, Lindner W.. Molecularly imprinted polymer-assisted sample clean-up of ochratoxin A from red wine: merits and limitations. J Chromatogr B Anal Technol Biomed Life Sci 2004; 804: 103-111
• 13 Turiel E, Tadeo JL, Cormack PAG, Martin-Esteban A.. HPLC imprinted-stationary phase prepared by precipitation polymerisation for the determination of thiabendazole in fruit. Analyst 2005; 130: 1601-1607
• 14 Kopp T, Abdel-Tawab M, Khoeiklang M, Mizaikoff B.. Development of a Selective Adsorbing Material for Binding of Pyrrolizidine Alkaloids in Herbal Extracts, Based on Molecular Group Imprinting. Planta Med 2019; 85: 1107-1113
• 15 Yan H, Row KH.. Characteristic and synthetic approach of molecularly imprinted polymer. Int J Mol Sci 2006; 7: 155-178
• 16 Schulz M, Meins J, Diemert S, Zagermann-Muncke P, Goebel R, Schrenk D, Schubert-Zsilavecz M, Abdel-Tawab M.. Detection of pyrrolizidine alkaloids in German licensed herbal medicinal teas. Phytomedicine 2015; 22: 646-656