NSAIDsare drugs with anti-inflammatory, analgesic and antipyretic effects. NSAID stands for "non-steroidal anti-inflammatory drug", they are non-steroidal anti-inflammatory drugs.

Inflammatory processes lead to the formation and release of substances that determine the development of symptoms (including pain). Therefore, many anti-inflammatory substances also have analgesic (pain-relieving) and antipyretic (fever-reducing) effects.

Drugs with anti-inflammatory (antiphlogistic) activity can be divided into two major groups: Corticosteroids, whose molecules have a steroid backbone, and NSAID's, whose molecules do not (hence the term "non-steroidal anti-inflammatory agents"). The chemical structures of NSAID's are heterogeneous. Most can be classified into the following four classes of compounds:

• Salicylic acid derivatives (e.g., aspirin).
• Propionic acid derivatives (e.g., ibuprofen)
• Pyrazole derivatives (pyrazolone and pyrazolidinedione derivatives)
• Aniline derivatives (incl. nicotinic and anthranilic acid derivatives)

If NSAID's are used, they can get into the organism and thus into animal foods.

Basically, there are no regulations for NSAID's in blood and urine in the regulation (EU) 37/2010, in which the maximum amounts (limits) for veterinary drug residues in food of animal origin are defined. Therefore, no limit values can be exceeded in these two matrices and only the detection of non-authorized substances such as mefenamic acid, phenylbutazone or ramifenazone can be objected to. For this reason, a large proportion of the tests are carried out in animal tissues and milk. Maximum residue limits in animal tissues exist for carprofen, diclofenac, flunixin, meloxicam, metamizole, tolfenamic acid and vedaprofen, but in milk only for flunixin, meloxicam and metamizole.

Some NSAID's are not suitable for routine or long-term use because of their toxicity (e.g., phenylbutazone or ramifenazone). Possible side effects include blood clotting disorders or tumor formation in animal studies. Therefore, no maximum residue limits could be established for these substances. They are therefore not considered approved for use in food-producing animals.

For the control of domestic foodstuffs for NSAIDs, there is an examination program within the framework of the National Residue Control Plan (NRKP) in the sense of preventive consumer protection, which comprises approx. 250 samples (muscle, milk and blood) per year.

Furthermore, samples are examined within the scope of actions of the official food control as well as in case of suspicion.

Spectrum of investigations and methods of analysis

In the Department of Veterinary Drugs, Hormones and Contaminants of the Institute of Food Safety Vienna we analyze NSAID's in animal matrices and are also National Reference Laboratory for these investigations.

Some NSAID's are metabolized in the organism to a good extent to metabolites: Metamizole to 4-methylaminoantipyrine, Flunixin to 5-hydroxyflunixin and Phenylbutazone to Oxyphenbutazone. Therefore, it is important that these metabolites can be determined by the analytical method used, especially since the limits in Regulation (EU) 37/2010 refer to 4-methylaminoantipyrine and 5-hydroxyflunixin (in milk).

Due to the great chemical diversity of NSAID's, two analytical methods (concerning sample preparation and measurement) covering different substances are used for the investigation:

• HPLC with mass spectrometric detection (LC-MSMS): for the majority of NSAID's in muscle, milk and blood samples.
• HPLC with diode array detection (HPLC-DAD): for pyrazolone derivatives in muscle samples

Sample types

Muscle, milk and blood samples are usually investigated.

Legal basis

Commission Regulation (EU) No. 37/2010 of 22 December 2009 on pharmacologically active substances and their classification with regard to maximum residue limits in foodstuffs of animal origin (OJ EU No. L 15 of 20.1.2010).