Development of a Selective Adsorbing Material for Binding of Pyrrolizidine Alkaloids in Herbal Extracts, Based on Molecular Group Imprinting

Abstract

Pyrrolizidine alkaloids are secondary plant constituents that became a subject of public concern because of their hepatotoxic, pneumotoxic, genotoxic, and cytotoxic effects. Due to disregardful harvesting and/or contamination with pyrrolizidine alkaloid-containing plants, there is a high risk of ingesting these substances with plant extracts or natural products. The limit for the daily intake was set to 0.007 µg/kg body weight. If contained in an extract, cleanup methods may help to minimize the pyrrolizidine alkaloid concentration. For this purpose, a material for depleting pyrrolizidine alkaloids in herbal preparations was developed based on the approach of molecular imprinting using monocrotaline. Molecular imprinted polymers are substances with specific binding characteristics, depending on the template used for imprinting. By means of group imprinting, only one molecule is used for creating selective cavities for many molecular pyrrolizidine alkaloid variations. Design of Experiment was used for the development using a 2⁵ screening plan resulting in 64 polymers (32 MIPs/32 NIPs). Rebinding trials revealed that the developed material can compete with common cation exchangers and is more suitable for depleting pyrrolizidine alkaloids than C₁₈- material. Matrix trials using an extract from Chelidonium majus show that there is sufficient binding capacity for pyrrolizidine alkaloids (80%), but the material is lacking in selectivity towards pyrrolizidine alkaloids in the presence of other alkaloids with similar functional groups such as berberine, chelidonine, and coptisine. Beyond this interaction, the selectivity could be proven for other structurally different compounds on the example of chelidonic acid.

Key words

pyrrolizidine alkaloids - molecular imprinting - design of experiment - Echium vulgare - Chelidonium majus - Papaveraceae - Boraginaceae

• References

• 1 Roeder E. Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie 1995; 50: 83-93
• 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 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: 648-656
• 8 Andersson LI, Paprica A, Arvidsson T. A highly selective solid phase extraction sorbent for pre-concentration of sameridine made by molecular imprinting. Chromatographia 1997; 46: 57-62
• 9 Theodoridis G, Manesiotis P. Selective solid-phase extraction sorbent for caffeine made by molecular imprinting. J Chromatogr A 2002; 948: 163-169
• 10 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
• 11 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
• 12 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
• 13 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
• 14 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