TY - JOUR A1 - Mugani, R. A1 - El Khalloufi, F. A1 - Kasada, M. A1 - Redouane, E. M. A1 - Haida, M. A1 - Aba, R. P. A1 - Essadki, Y. A1 - Zerrifi, S. E. A. A1 - Herter, Sven-Oliver A1 - Hejjaj, A. A1 - Aziz, F. A1 - Ouazzani, N. A1 - Azevedo, J. A1 - Campos, A. A1 - Putschew, A. A1 - Grossart, H.-P. A1 - Mandi, L. A1 - Vasconcelos, V. A1 - Oudra, B. T1 - Monitoring of toxic cyanobacterial blooms in Lalla Takerkoust reservoir by satellite imagery and microcystin transfer to surrounding farms N2 - Cyanobacterial harmful algal blooms (CyanoHABs) threaten public health and freshwater ecosystems worldwide. In this study, our main goal was to explore the dynamics of cyanobacterial blooms and how microcystins (MCs) move from the Lalla Takerkoust reservoir to the nearby farms. We used Landsat imagery, molecular analysis, collecting and analyzing physicochemical data, and assessing toxins using HPLC. Our investigation identified two cyanobacterial species responsible for the blooms: Microcystis sp. and Synechococcus sp. Our Microcystis strain produced three MC variants (MC-RR, MC-YR, and MC-LR), with MC-RR exhibiting the highest concentrations in dissolved and intracellular toxins. In contrast, our Synechococcus strain did not produce any detectable toxins. To validate our Normalized Difference Vegetation Index (NDVI) results, we utilized limnological data, including algal cell counts, and quantified MCs in freeze-dried Microcystis bloom samples collected from the reservoir. Our study revealed patterns and trends in cyanobacterial proliferation in the reservoir over 30 years and presented a historical map of the area of cyanobacterial infestation using the NDVI method. The study found that MC-LR accumulates near the water surface due to the buoyancy of Microcystis. The maximum concentration of MC-LR in the reservoir water was 160 μg/L. In contrast, 4 km downstream of the reservoir, the concentration decreased by a factor of 5.39 to 29.63 μg/L, indicating a decrease in MC-LR concentration with increasing distance from the bloom source. Similarly, the MC-YR concentration decreased by a factor of 2.98 for the same distance. Interestingly, the MC distribution varied with depth, with MC-LR dominating at the water surface and MC-YR at the reservoir outlet at a water depth of 10 m. Our findings highlight the impact of nutrient concentrations, environmental factors, and transfer processes on bloom dynamics and MC distribution. We emphasize the need for effective management strategies to minimize toxin transfer and ensure public health and safety. KW - Cyanotoxin KW - HPLC-MS/MS KW - Surface water PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-623672 DO - https://doi.org/10.1016/j.hal.2024.102631 SN - 1568-9883 VL - 135 SP - 1 EP - 14 PB - Elsevier CY - Amsterdam AN - OPUS4-62367 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Herter, Sven-Oliver A1 - Koch, Matthias A1 - Haase, Hajo T1 - First Synthesis of Ergotamine-13CD3 and Ergotaminine-13CD3 from Unlabeled Ergotamine N2 - Ergot alkaloids (EAs) formed by Claviceps fungi are one of the most common food contaminants worldwide, affecting cereals such as rye, wheat, and barley. To accurately determine the level of contamination and to monitor EAs maximum levels set by the European Union, the six most common EAs (so-called priority EAs) and their corresponding epimers are quantified using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The quantification of EAs in complex food matrices without appropriate internal tandards is challenging but currently carried out in the standard method EN 7425:2021 due to their commercial unavailability. To address the need for isotopically labeled EAs, we focus on two semi-synthetic approaches for the synthesis of these reference standards. Therefore, we investigate the feasibility of the N6-demethylation of native ergotamine to yield norergotamine, which can subsequently be remethylated with an isotopically labeled methylating reagent, such as iodomethane (13CD3-I), to yield isotopically labeled ergotamine and its C8-epimer ergotaminine. Testing the isotopically labeled ergotamine/-inine against native ergotamine/-inine with HPLC coupled to high-resolution HR-MS/MS proved the structure of ergotamine-13CD3 and ergotaminine-13CD3. Thus, for the first time, we can describe their synthesis from unlabeled, native ergotamine. Furthermore, this approach is promising as a universal way to synthesize other isotopically labeled EAs. KW - Reference Material KW - HPLC-MS/MS KW - Mycotoxins KW - Standards KW - Organic Synthesis KW - Isotope PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-600167 DO - https://doi.org/10.3390/toxins16040199 VL - 16 IS - 4 SP - 1 EP - 12 PB - MDPI AN - OPUS4-60016 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Quantifizierung von Mutterkornalkaloiden in Lebensmitteln unter Verwendung neu entwickelter stabil isotopenmarkierter interner Standards N2 - Mutterkornalkaloide sind Mykotoxine, die von Pilzen der Gattung Claviceps produziert werden und häufig in Roggen- und Weizenprodukten vorkommen. Aufgrund ihrer toxikologischen Relevanz hat die Europäische Union im Jahr 2022 erstmals Grenzwerte für diese Alkaloide in Lebensmitteln eingeführt. Eine zuverlässige Quantifizierung ist essenziell für die Überwachung der Lebensmittelsicherheit. Allerdings stellte der bisherige Mangel an stabilen isotopenmarkierten (SIL - stable isotopically labeled) Standards eine wesentliche Herausforderung für die Entwicklung präziser Analysemethoden mittels HPLC-MS/MS dar. Um diese Lücke zu schließen, wurden erstmals alle zwölf prioritären Mutterkornalkaloide über einen einheitlichen Semisyntheseansatz als 13CD3-markierte Analoga synthetisiert und als interne Standards für die massenspektrometrische Analyse eingesetzt. Die Quantifizierung erfolgte mittels HPLC-MS/MS in verschiedenen Lebensmittelmatrizes, darunter Brot, Roggen- und Weizenmehl sowie Kleie. Zur Evaluierung der SIL-Standards wurden etablierte Methoden wie externe Kalibrierung und Standardaddition herangezogen. Die Studienergebnisse zeigen, dass der Einsatz von SIL-Standards die Genauigkeit und Präzision der Mutterkornalkaloid-Quantifizierung signifikant verbessert. Dies ist insbesondere auf die Korrektur von Matrixeffekten, Extraktions- und Signalschwankungen während der massenspektrometrischen Analyse zurückzuführen. Die neu synthetisierten 13CD3 markierten Mutterkornalkaloide stellen daher ein wertvolles Werkzeug zur Verbesserung der Lebensmittelsicherheit dar, da sie zuverlässigere und reproduzierbare Messergebnisse ermöglichen. Darüber hinaus leisten diese Ergebnisse einen wichtigen Beitrag zur Weiterentwicklung analytischer Methoden zur Überwachung von Mutterkornalkaloiden und damit zur Sicherstellung der Lebensmittelqualität. T2 - 53. Deutsche Lebensmittelchemietage CY - Halle a.d. Saale, Germany DA - 22.09.2025 KW - HPLC-MS/MS KW - Interner Standard KW - Qualitätssicherung PY - 2025 AN - OPUS4-64546 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Herter, Sven-Oliver A1 - Haase, Hajo A1 - Koch, Matthias T1 - Semisynthesis of Stable Isotope-Labeled Ergot Alkaloids for HPLC-MS/MS Analysis N2 - Ergot alkaloids (EAs) are prevalent food contaminants affecting cereals, such as rye, wheat, and barley worldwide. To ensure EU safety standards, the six most common EAs: ergometrine, ergotamine, ergosine, ergocornine, ergocristine, and ergocryptine, and their epimers, are quantified using HPLC-MS/MS, as described in the European Standard Method EN 17425:2021. However, this can be challenging and time-consuming in food matrices without appropriate internal standards and highlights the need for more robust and precise analytical tools to support their monitoring. The development of isotope-labeled EAs directly addresses this gap, offering improved accuracy and leading to more consistency across laboratories and consequently to more consumer safety. Therefore, we developed a semisynthetic approach, building upon our previous work where native ergotamine was N6-demethylated to norergotamine and subsequently remethylated using iodomethane (13CD3-I). Herein, we are now able to present the successful synthesis of all of the isotopically labeled priority EAs. These isotope-labeled standards were tested against their native counterparts using HPLC coupled with HR-MS/MS. The chromatographic and mass spectrometric properties of the unlabeled and isotopically labeled EAs match exactly, confirming their successful synthesis and structure. These standards can now be utilized to enhance the accuracy and reliability of EA quantification in food and feed. KW - Reference Material KW - HPLC-MS/MS KW - Mycotoxins KW - Ergot Alkaloids KW - Stable Isotope Dilution Analysis KW - Semisynthesis PY - 2025 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-639692 DO - https://doi.org/10.1021/acs.jafc.5c03345 SN - 0021-8561 VL - 73 IS - 29 SP - 18412 EP - 18419 PB - American Chemical Society (ACS) AN - OPUS4-63969 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Semi-synthesis of isotopic labeled ergot alkaloids: New reference standards N2 - We developed a two-step semi-synthesis for the preparation of isotopically labeled EAs, starting from native EAs. This universal strategy enabled the successful synthesis of all isotopically labeled priority EAs. The structure of the isotopically labeled EAs was confirmed by HPLC-HR-MS/MS using native, unlabeled EAs as a reference standard. The next step will be the implementation of the isotopically labeled standards in the European standard procedure EN 17425 to improve the quantification of EAs in foodstuffs. T2 - 45th Mycotoxin Workshop CY - Vienna, Austria DA - 02.06.2024 KW - Reference Material KW - HPLC-MS/MS KW - Mycotoxins KW - Isotop standards KW - Organic Synthesis KW - Ergot alkaloids PY - 2024 AN - OPUS4-60239 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - New PFAS Reference Materials for Environment and Circular Economy N2 - Per- and polyfluorinated alkyl substances (PFAS) are a group of synthetic compounds that have been used in various industrial and consumer products for decades. Their wide range of applications is due to water- and oil-repellent properties, as well as their chemical and thermal stability. However, the use of PFAS has raised concerns due to their persistence in environment and their adverse health effects, leading to regulations aimed at controlling their use and minimizing exposure. Substances such as PFOS, PFHxS, and PFOA are listed in the Stockholm Convention on Persistent Organic Pollutants (POP Regulation, EU 2019/1021). Maximum values have been set for PFAS in environmental matrices such as soil and water, but also for textiles as a relevant area of circular economy and part of the current German standardization roadmap “Circular Economy”. Reliable PFAS analysis requires an increasing global demand for certified reference materials (CRM). However, CRMs for PFAS in soils and textiles are rare or currently not available. To improve the metrological infrastructure and support PFAS measurements, two CRMs for PFAS in soil (BAM-U027) and PFAS in textiles (BAM-B003) based on ISO 17034 and ISO 33405 were developed. This poster provides an overview of the different steps for preparation and characterization of the two candidate materials. The assignment of the certified mass fractions for relevant PFAS targets (18 PFAS targets for BAM-B003) is based isotope dilution HPLC-MS/MS at three independent workplaces. The results of the BAM in-house study on BAM-U027 were supported by an interlaboratory comparison study. T2 - 16th International Symposium on Biological and Environmental Reference Materials CY - Halifax, Nova Scotia, Canada DA - 01.06.2025 KW - Certified Reference Material KW - PFAS KW - Circular Economy KW - Textiles KW - Quality assurance PY - 2025 AN - OPUS4-63404 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Synthesis and application of isotopic labelled ergot alkaloids N2 - Ergot alkaloids form a toxicologically relevant group of mould toxins (mycotoxins) that are among the most common contaminants of foodstuff and animal feed worldwide. Reliable controls are essential to minimise health risks and economic damage. Due to their toxicological relevance, EU limit values for 12 priority ergot alkaloids have been introduced for the first time in 2022 and range from 500 μg/kg in rye milling products down to 20 ug/kg Processed cereal-based foods for infants and young children[1]. High-performance liquid chromatography - mass spectrometry is used to quantify low concentrations of ergots in food, however the European standard analytical procedure cannot be applied due to the lack of isotopically labelled reference standards. The complex structure of the ergot alkaloids makes a total synthesis extremely challenging, expensive and time-consuming. Therefore, we are focusing on different semi-preparative methods (electrochemistry, organic synthesis, heterogeneous catalysis) to specifically N-demethylate the C8 carbon atom of the lysergic acid moiety. The norergot alkaloid formed is then isotopically labelled using an electrophilic methyl source, i.e. iodomethane or dimethyl sulphate to obtain the specific isotopic labelled ergot alkaloid. Initial experiments have shown that N-demethylation of the ergot alkaloid ergotamine is possible by both electrochemical and wet-chemical organic synthesis. The next step is to improve the previously determined reaction conditions to enable the synthesis of norergotamine on a mg scale for further reactions. T2 - ISEAC-41 CY - Amsterdam, Netherlands DA - 20.11.2023 KW - Reference Material KW - Isotope KW - Standards KW - Mykotoxine KW - HPLC-MS PY - 2023 AN - OPUS4-59315 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Quantifying Ergot Alkaloids in Food Using Newly Developed Stable Isotope-Labeled Standards N2 - Ergot alkaloids are a class of mycotoxins produced by fungi of the Claviceps genus, which are commonly found in contaminated cereals. Due to their toxic effects, the European Union introduced the first regulatory limit values for ergot alkaloids in food in 2022. Accurate quantification is crucial for food safety monitoring; however, the lack of stable isotopically labeled (SIL) standards has been a major limitation in the development of analytical methods via HPLC-MS/MS. In order to overcome this challenge, all 12 priority ergot alkaloids were synthesized as 13CD3-labeled analogues for the first time and used as internal standards for mass spectrometry-based analysis. Using HPLC-MS/MS, we quantified ergot alkaloids in various food matrices, including bread, rye – and wheat flour, and bran. The performance of the SIL standards was evaluated by comparing results obtained using external calibration and standard addition approaches. Our study demonstrates that the use of SIL standards significantly improves the accuracy and precision of ergot alkaloid quantification by correcting for matrix effects and signal variations in mass spectrometric analysis. The newly synthesized 13CD3-labeled ergot alkaloids provide a valuable tool for food safety assessments, ensuring more reliable and reproducible data. Furthermore, these findings support the advancement of analytical methods for ergot alkaloid monitoring, contributing to improved food quality control and regulatory compliance. T2 - 16th International Symposium on Biological and Environmental Reference Materials CY - Halifax, Nova Scotia, Canada DA - 01.06.2025 KW - Reference Material KW - HPLC-MS/MS KW - Metrology KW - Stable isotope dilution analysis KW - Quality assurance KW - Ergot alkaloids KW - Food Safety PY - 2025 AN - OPUS4-63409 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Synthesis and application of stable isotopically labeled ergot alkaloids N2 - Ergot alkaloids form a toxicologically relevant group of mold toxins (mycotoxins) that are among the most common contaminants of food and animal feed worldwide. Therefore, reliable controls are indispensable for the minimization of both health risks and economic damages. As a consequence of their toxicological significance, EU limit values for 12 priority ergot alkaloids were established for the first time in 2022. These limits range from 500 µg/kg in rye milling products down to 20 µg/kg in processed cereal-based foods for infants and young children. Despite the use of high-performance liquid chromatography-mass spectrometry to quantify low concentrations of ergots in food, the current European standard procedure EN 17425:2021 cannot be fully applied due to the lack of isotopically labeled reference standards. The complex structure of the ergot alkaloids makes a total synthesis extremely challenging, expensive, and time-consuming. Consequently, we focused on a semi-synthetic approach with the aim of specifically demethylating the N6-atom of the lysergic acid moiety, a shared structural feature among all ergot alkaloids. This resulted in the formation of a norergot alkaloid, which was purified using preparative HPLC. The reaction of the norergot alkaloid with an isotopically labeled electrophilic methyl source, such as iodomethane or dimethyl sulfate, yielded the desired isotopically labeled ergot alkaloid. This methodology enabled the successful synthesis of all 12 stable isotopically labeled priority ergot alkaloids for the first time. Herein we present the problem of the current unavailability of these isotopically labeled standards and our approach to solve this urged demand. Moreover, we are able to present initial data on how these standards enhance the European standard procedure, EN 17425:2021. T2 - 11th International Symposium on RECENT ADVANCES IN FOOD ANALYSIS CY - Prague, Czech Republic DA - 05.11.2024 KW - Reference Material KW - HPLC-MS/MS KW - Mycotoxins KW - Ergot Alkaloids KW - Isotopic Labeling PY - 2024 AN - OPUS4-61690 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Synthesis and application of isotopic labelled ergot alkaloids N2 - Ergot alkaloids form a toxicologically relevant group of mould toxins (mycotoxins) that are among the most common contaminants of food and animal feed worldwide. Reliable controls are essential to minimise health risks and economic damage. Due to their toxicological relevance, EU limit values for 12 priority ergot alkaloids have been introduced for the first time in 2022 and range from 500 µg/kg in rye milling products down to 20 ug/kg Processed cereal-based foods for infants and young children[1]. High-performance liquid chromatography - mass spectrometry is used to quantify low concentrations of ergots in food, however the European standard analytical procedure cannot be applied due to the lack of isotopically labelled reference standards. The complex structure of the ergot alkaloids makes a total synthesis extremely challenging, expensive and time-consuming. Therefore, we are focusing on different semi-preparative methods (electrochemistry, organic synthesis, heterogeneous catalysis) to specifically N-demethylate the C8 carbon atom of the lysergic acid moiety. The norergot alkaloid formed is then isotopically labelled using an electrophilic methyl source, i.e. iodomethane or dimethyl sulphate to obtain the specific isotopic labelled ergot alkaloid. Initial experiments have shown that N-demethylation of the ergot alkaloid ergotamine is possible by both electrochemical and wet-chemical organic synthesis. The next step is to adapt the previously determined reaction conditions to enable the synthesis of norergotamine on a mg scale. T2 - 41. International Conference on Environmental & Food Monitoring CY - Amsterdam, Netherlands DA - 20.11.2023 KW - Reference materials KW - Metrology KW - Isotope dilution analysis KW - Calibration standards PY - 2023 AN - OPUS4-59234 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Quantifying ergot alkaloids in food using stable isotopically labeled standards N2 - Ergot alkaloids (EAs) are toxic secondary metabolites produced by fungi of the genus Claviceps. They grow on rye and wheat, and are introduced into the food chain through the harvest of infected cereals. Therefore, the European Union has established a maximum level for the 12 most abundant EAs. In order to improve the quantification, stable isotopically labelled EAs were synthesized for the first time and their performance was evaluated in comparison to the current European standardmethod in different foodstuff. T2 - ANAKON 2025 CY - Leipzig, Germany DA - 10.03.2025 KW - Reference Material KW - HPLC-MS/MS KW - Mycotoxins KW - Standards KW - Stable Isotope Dilution Analysis PY - 2025 AN - OPUS4-62752 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Herter, Sven-Oliver T1 - Isotopically labeled ergot alkaloids: A step toward safer foodstuffs N2 - Ergot alkaloids form a toxicologically relevant group of mold toxins (mycotoxins) that are among the most common contaminants of food and animal feed worldwide. It is therefore imperative that reliable controls are necessary in order to minimize both the health risks and the economic damage. In consequence of their toxicological relevance, EU limit values for 12 priority ergot alkaloids were established for the first time in 2022. These limits range from 500 µg/kg in rye milling products down to 20 µg/kg in processed cereal-based foods for infants and young children. Despite the use of high-performance liquid chromatography-mass spectrometry to quantify low concentrations of ergots in food, the European standard analytical procedure cannot be fully applied due to the unavailability of isotopically labeled reference standards. The complex structure of the ergot alkaloids makes a total synthesis extremely challenging, expensive, and time-consuming. Consequently, we focused on a semi-synthetic approach with the aim of specifically demethylating the N6-atom of the lysergic acid moiety, a shared structural feature among all ergot alkaloids. This resulted in the formation of a norergot alkaloid, which was purified using preparative HPLC. The reaction of the norergot alkaloid with an isotopically labeled electrophilic methyl source, such as iodomethane or dimethyl sulfate, yielded the desired isotopically labeled ergot alkaloid. This methodology enabled the successful synthesis of all 12 stable isotopically labeled priority ergot alkaloids worldwide for the first time. Herein we present the problem of unavailability of these isotopically labeled standards and our approach to solve this urged demand. T2 - Adlershofer Forschungsforum CY - Berlin, Germany DA - 11.11.2024 KW - Reference Material KW - HPLC-MS/MS KW - Mycotoxins KW - Ergot Alkaloids KW - Isotopic Labeling PY - 2024 AN - OPUS4-61691 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -