Only a few tranquillizers appear in Regulation (EU) No. 37/2010, in which the classification of pharmacologically active substances regarding maximum residue limits in foodstuffs of animal origin is set out:
Approved drugs include azaperone, with a cumulative threshold limit for azaperone together with its metabolite azaperol, carazolol (this is the marker residue, as the metabolites have no pharmacological activity) and xylazine, for which no maximum residue limit is required.
Banned substances: chlorpromazine
Non-approved tranquillizers are substances that are not listed in Regulation (EU) 37/2010. These are not permitted for use in animals intended for human consumption. They include acepromazine, haloperidol and propionylpromazine.
Some foreign substances (including, for example, medicines) are chemically modified in the organism by enzymes. Phenothiazines, for example, form a large number of metabolites: the ring system and the side chain may first be hydroxylated, then conjugated with glucuronic acid, the tertiary amine can be N-dealkylated and the sulphur atom oxidised to sulfoxide.
Xylazine is metabolised very quickly in the liver and excreted via the kidneys (70%) and the gall bladder (30%). Its half-life in the plasma is 1 to 6 minutes.
If metabolic reactions take place to a not inconsiderable extent, not only the original drugs (parent substances), but also their metabolites are defined as marker residues in Regulation (EU) 37/2010 and cumulative limits are set for these (see above: azaperone).
Analyses and range of tests
The Department of Veterinary Drugs, Hormones and Cont0aminants at the Institute for Food Safety in Vienna analyses tranquillizers in animal tissue and is also the National Reference Laboratory for these tests.
After suitable sample preparation, the following tranquillizers are analysed using high pressure liquid chromatography with a diode array (HPLC/DAD) or with mass spectrometer detection (LC/MS-MS):
- Azaperone and azaperol
The highest tranquilizer concentrations are mostly found in the kidneys. Kidney samples are therefore routinely analysed, and in rare case muscle samples as well.