Tropane Alkaloids

1. Introduction

Tropane alkaloids are secondary metabolites characterized by the 8-azabicyclo octane nucleus and are commonly present in plants of Brassicaceae, Solanaceae, Convolvulaceae, and Erythroxylaceae. There are more than 200 different TAs identified. The most common tropane alkaloids are atropine, hyoscyamine, and scopolamine ⁽¹⁾. Plant extracts containing tropane alkaloids have been used for over a century, for both medicine-related applications and recreationally. However, a number of these metabolites are toxic and have been known to cause severe illnesses, intoxication, and even death, so testing for tropane alkaloid compounds is crucial. Some crops produce tropane alkaloids on their own, but most contaminated food crops pick up the toxins when they are co-harvested with nearby weeds that contain them ⁽²⁾.

Data Source: Monographs of the European Scientific Cooperative on Phytotherapy (ESCOP); European Pharmacopoeia 8.0

2. Industrial significance ^(1,3)

Medicinal plants of the Solanaceae produce a unique class of metabolites called tropane alkaloids (TAs), some of which have potent anticholinergic activity. Hyoscyamine and scopolamine are known medicinal tropane alkaloids and anticholinergic drugs. These drugs are clinically used to treat asthma, pain, motion sickness, functional gastrointestinal disorders, Parkinson’s syndrome, and others. Hyoscyamine is an important material for industrially producing ipratropium bromide and scopolamine for tiotropium bromide. Ipratropium bromide and tiotropium bromide are essential drugs in the treatment of chronic obstructive pulmonary disease. Therefore, the demand for the two alkaloids is huge In contrast, the cultivation and production of scopolamine is of major economic interest due to its miscellaneous pharmaceutical applications. Therefore, global demand for this compound is increasing. Moreover, scopolamine is one of the most essential medicines of the World Health Organization (WHO). Hyoscyamine and scopolamine are obtained from the Duboisia plants being cultivated on large plantations in Queensland, Australia. Climate change causes new biotic and abiotic factors that challenge the pharmaceutical industry and food industry to produce consistently high volumes of scopolamine.

3. Regulation and Limits⁽⁶⁾

Tropane alkaloids (TPA) are important natural products that are found in plants across the world and occur mostly in the Solanaceae family. Atropine, hyoscyamine, scopolamine, and cocaine are examples of anticholinergic drugs. According to the European Food Safety Authority (EFSA), tropane alkaloids are of particular toxicological relevance in cereals and cereal-based baby foods, buckwheat, soy products, herbal teas, and oilseeds such as flax and sunflower seeds. These products may be contaminated by the seeds of certain plants containing tropane alkaloids.  New Regulation (EU) 2021/1408 amends Regulation (EC) No. 1881/2006 as regards the maximum levels of tropane alkaloids in certain foodstuffs. The new regulation became applicable on September 19, 2021. The already applicable maximum levels for atropine and scopolamine of 1 µg/kg each in cereal-based foods containing millet, sorghum millet, or buckwheat have been extended to cereal-based foods containing maize. For a person weighing 65 kg, this calculates to a total safe intake of 1.04 µg of atropine and scopolamine. A total safe intake of 0.32 g of atropine and scopolamine for a preschool child weighing 20 kg has been calculated.

4. Testing Methods ⁽⁴⁾

The development of appropriate analytical methods has great importance for the determination of these compounds, including extraction and clean-up steps, separation by chromatographic techniques, and detection by mass spectrometry (MS). In this sense, the newly developed methods, as proposed by the European Commission, should preferably be HPLC-MS or GC-MS in the event that HPLC-MS is not available. The optimized and validated methods must reach quantification limits of less than 5 µg/kg for agricultural products, ingredients, food supplements, and infusions; 2 µg/kg for final products; and 1 µg/kg for baby.

5. Eurofins Services in Tropane Alkaloid testing ⁽⁵⁾

Our experts from the Competence Centre for Mycotoxins & Biotoxins offer the analysis of the most important tropane alkaloids atropine (sum of (+)- and (-)-hyoscyamine) and scopolamine in all relevant food and feed matrices via LC-MS/MS. Requirements regarding the limit of quantification given in the EU documents are fulfilled. In addition to atropine and scopolamine, Eurofins offers now the analysis of anisodamine, norscopolamine and convolvine in tea and herbal tea.

References:

1. González-Gómez, Lorena, et al. "Occurrence and Chemistry of Tropane Alkaloids in Foods, with a Focus on Sample Analysis Methods: A Review on Recent Trends and Technological Advances." Foods3 (2022): 407.
2. Samson Afewerki, Jia-Xin Wang, Wei-Wei Liao, Armando Córdova, The Chemical Synthesis and Applications of Tropane Alkaloids; Hans-Joachim Knölker; The Alkaloids: Chemistry and Biology, Academic Press, 81, 2019, 151-233.
3. Kohnen-Johannsen KL, Kayser O. Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production. Molecules. 2019 Feb 22;24(4):796. doi: 10.3390/molecules24040796. PMID: 30813289; PMCID: PMC6412926.
4. https://emedicine.medscape.com/article/816657-overview
5. https://cdnmedia.eurofins.com/corporate-eurofins/media/12151537/tropanalkaloids.pdf
6. https://eur-lex.europa.eu/eli/reg/2021/1408/oj

Contact Us