What are NSAIDs?
Drugs with anti-inflammatory (antiphlogistic) action can be divided into two major groups:
Corticosteroids, whose molecules have a steroid core structure and
NSAIDs, whose molecules have no such structure (hence the designation “nonsteroidal anti-inflammatory drugs”).
Inflammatory processes lead to the formation and release of substances which are decisive for the development of symptoms (including pain). Thus many of these substances also have a pain-relieving (analgesic) and fever-reducing (antipyretic) effect. Prostaglandins - metabolites of arachidonic acid - play a central role in the biochemistry of inflammatory activity. The mechanisms of action of the two groups of anti-inflammatory drugs are different: corticosteroids prevent the synthesis of arachidonic acid, while NSAIDs intervene one stage later, in the majority of cases inhibiting the cyclooxygenase activity that is responsible for the formation of prostaglandins.
The chemical structures of NSAIDs are heterogeneous. Most of them can be allocated to the following four classes of compound:
- Salicylic acid derivatives (e.g. aspirin)
- Propionic acid derivatives (e.g. ibuprofen)
- Pyrazole derivatives (pyrazolone and pyrazolidindione derivatives)
- Aniline derivatives (including nicotinic acid (niacin) and anthranilic acid derivatives)
In principle there are no provisions for blood and urine in Regulation (EU) 37/2010, in which maximum levels (limits) are set for veterinary drug residues in foodstuffs of animal origin. Therefore, there can be no exceedances of limits with regard to these matrices and only the detection of unauthorised substances such as mefenamic acid, phenylbutazone or ramifenazone can be flagged.
For this reason, the majority of tests are carried out on animal tissues and milk. Maximum residue levels in animal tissue exist for carprofen, diclofenac, flunixin, meloxicam, metamizole, tolfenamic acid and vedaprofen yet in milk only for flunixin, meloxicam and metamizole.
Due to their toxicity, some NSAIDs are not suitable for either routine or for long-term use (e.g. phenylbutazone or ramifenazone). Possible side effects include blood coagulation defects or formation of tumours in animal testing. No maximum residue levels could therefore be set for these substances. Thus they are not permitted for use in food-producing animals.
Range of testing and methods of analysis
The Department of Veterinary Drugs, Hormones and Contaminants at the Institute for Food Safety in Vienna analyses NSAIDs in a wide variety of sample types and is also the National Reference Laboratory for these tests and investigations.
Due to the great chemical diversity of NSAIDs, two analytical procedures (with regard to sample preparation and measurement) that each cover different substances are used when testing:
- HPLC with mass spectrometric detection (LC/MS-MS):
Carprofen (propionic acid derivative)
Diclofenac (anthranilic acid derivative)
Flufenamic acid (anthranilic acid derivative)
Flunixin and its metabolite 5-hydroxyflunixin (nicotinic acid derivatives)
Ibuprofen (propionic acid derivative)
Ketoprofen (propionic acid derivative)
Meclofenamic acid (anthranilic acid derivative)
Mefenamic acid (anthranilic acid derivative)
Meloxicam (oxicam derivative)
Naproxen (propionic acid derivative)
Niflumic acid (anthranilic acid derivative)
Phenylbutazone and its metabolite oxyphenbutazone (pyrazolidindione derivatives)
Tolfenamic acid (anthranilic acid derivative)
Vedaprofen (propionic acid derivative)
- HPLC with diode array detection (HPLC/DAD):
4-Methylaminoantipyrine (marker residue of metamizole)
Isopropyl aminoantipyrine (ramifenazone, isopyrin)
Muscle, kidney, milk and blood samples are usually tested.
Commission Regulation (EU) 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin (OJ EU No. L 15 of 20/1/2010).