New legal regulations for unauthorised veterinary drugs
New validated methods for the safety of your products in compliance with all regulatory requirements
Apr 2023. Since the end of 2022, lower reference points for action (RPAs) defined in Regulation (EU) 2019/1871 apply to chloramphenicol, malachite green, and nitrofurans and their metabolites[1]. Additionally, a new RPA has been added for 3,5-dinitrosalicylic acid hydrazide (DNSH), the metabolite of nifursol. The RPA is the lowest value that can be achieved by analysis in official control laboratories, as there are no maximum residue limits for the unauthorised substances.
Our experts of the Eurofins Competence Centre for Veterinary Drug Residues have optimised our methods to reliably quantify all the compounds mentioned above, including DNSH, below or at the RPA in a wide matrix variety. Our methods are accredited, validated and meet the performance requirements for official controls.
Banned antibiotics
Nitrofurans are used as antimicrobials and are explicitly prohibited in the European Union for food-producing animals. Since they are rapidly metabolised, they are found in tissues as protein- or DNA-bound metabolites. In milk, parent substances such as nitrofurazone are also still detectable after antibiotic administration. Both parent compounds and metabolites have been linked to the development of a wide range of acute and chronic toxic effects (e.g. neurotoxicity and embryotoxicity) and other diseases[2].
In addition, the broad-spectrum antibiotic chloramphenicol (CAP) is prohibited in the EU for food-producing animals. In humans, CAP can cause irreversible bone marrow damage, amongst other effects. It also causes reproductive and hepatotoxic effects in animals[3].
Pharmacologically active dyes
Malachite green dyes, also known as triphenylmethane dyes, are frequently used in aquaculture for their antifungal and antiprotozoal effects to prevent fish diseases, especially in non-EU countries. However, malachite green and its metabolite leucomalachite green are not only environmental pollutants but also potentially carcinogenic and/or genotoxic substances[4]. Therefore, they are prohibited in the EU. Residues must not be present in animal foods. In addition to malachite green, crystal violet and brilliant green are also counted among these dyes. There is no legally binding RPA on the latter. However, the European Reference Laboratory (EURL) has published corresponding minimum method performance requirements (MMPR), which should be adhered to, especially for official testing[5].
New control levels for the detection of prohibited substances:
Substance |
Control levels [µg/kg] |
Other provisions |
| Banned amphenicols 1 | ||
| Chloramphenicol | 0.15* | |
| Metabolites of nitrofurans | ||
| SEM (semicarbazide) 2 | 0.5* | as metabolite of nitrofurazone |
| AHD (1-aminohydantoin) | 0.5* | as metabolite of nitrofurantoin |
|
AMOZ (3-amino-5-methylmorpholino-2-oxazolidinone) |
0.5* | as metabolite of furaltadone |
| AOZ (3-amino-2-oxazolidinone) | 0.5* | as metabolite of furazolidone |
| DNSH (3,5-dinitrosalicylic acid hydrazide) | 0.5* | as metabolite of nifursol |
| Malachite dyes | ||
|
Malachite green |
0.5* | for the sum of malachite green und leucomalachite green |
| Crystal violet (Gentian violet) | 0.5** | for the sum of crystal violet und leucocrystal violet |
| Brilliant green | 0.5** | for the sum of brilliant green und leucobrilliant green 3 |
* Reference point for action (RPA) according to Regulation (EU) 2019/1871[1].
** Minimum method performance requirements, MMPR of the EURLs[5].
1 Only explicitly prohibited amphenicols are listed according to the Annex of Regulation (EU) 37/2010, Table 2.
2 Does not apply to crayfish with natural SEM content.
3 Only brilliant green is analysed, leucobrilliant green will be included in the analysis spectrum soon (control was not mandatory as long as no reference standard was available on the market).
Analysis and legal requirements
Quantitative confirmatory methods must be able to reliably determine values at the RPA for non-authorised substances. If no RPA has been defined, the determination of prohibited or non-authorised substances should be carried out at a concentration as low as achievable according to the ALARA principle ("as low as reasonably achievable"). The MMPR values of the EURLs are used as technical guidance[5].
Our LC-MS/MS methods allow the unambiguous identification and quantification of the unauthorised veterinary drugs in the lowest concentration ranges. They are validated according to Regulation (EU) 2021/808[6] and meet the strict performance requirements for official controls. The methods for dyes and all regulated nitrofuran metabolites as well as CAP are in principle suitable for all animal matrices. Please contact us for specific product enquiries. In addition, we offer direct detection of nitrofurazone for milk and dairy products.
Our experts of the Competence Centre for Veterinary Drug Residues have many years of experience with LC-MS/MS analysis of more than 250 veterinary drugs in all relevant food and feed matrices. Due to our designation as an official laboratory according to Art. 37 (1) of Regulation (EU) 2017/625, we also offer the analysis of official samples on behalf of European Authorities.
Contact us
Do you have questions about the analysis of veterinary drug residues? Contact your personal account manager or our expert Roma Nemitz-Sturm directly.
Relevant Sources
[1] Commission Regulation (EU) 2019/1871 on reference points for action for non-allowed pharmacologically active substances present in food of animal origin
[2] EFSA Panel on Contaminants in the Food Chain (CONTAM), 2015. Scientific Opinion on nitrofurans and their metabolites in food. EFSA Journal, 13(6), 4140
[3] EFSA Panel on Contaminants in the Food Chain (CONTAM), 2014. Scientific Opinion on Chloramphenicol in food and feed. EFSA Journal, 12(11), 3907
[4] EFSA Panel on Contaminants in the Food Chain (CONTAM), 2016. Scientific Opinion on Malachite green in food. EFSA Journal, 14(7), 4530
[5] European Union Reference Laboratories, 2022. EURL Guidance on Minimum Method Performance Requirements (MMPRs) for specific pharmacologically active substances in specific animal matrices. Version 2.0
[6] Commission Implementing Regulation (EU) 2021/808 on the performance of analytical methods for residues of pharmacologically active substances used in food-producing animals and on the interpretation of results as well as on the methods to be used for sampling
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