Antiparasitics are drugs that are used against parasites. Parasites reside either in the body of the host (e.g. worms) or on the body surface (e.g. ticks, fleas, mites). Antiparasitics are used in veterinary medicine to counteract an infestation of parasites.

Many antiparasitics can be assigned to the following chemical compound classes:

• Avermectins: effective against both endo- and ectoparasites.
• Benzimidazoles and imidazothiazoles (levamisole): effective against endoparasites
• Salicylic acid/phenol derivatives (incl. salicylanilides)/benzenesulfonamides: active against endoparasites
• Organophosphate compounds and pyrethroids: act against ectoparasites

If antiparasitics are used, they can enter the organism and thus animal food.

Legal regulation

For animal tissues (muscle, fat, liver and kidneys), partly for milk and for eggs (flubendazole), there are limits in Regulation (EU) 37/2010, which sets maximum residue limits for veterinary medicinal products in food of animal origin. These, as with most other drugs, are much lower for milk than for the other matrices. Administration of some antiparasitics (e.g., mebendazole) is specifically prohibited in milk-producing animals. Blood and urine are not regulated in the above regulation.

Many foreign substances (e.g. also drugs) are chemically modified in the organism by enzymes. Therefore, for many drugs, not only the original substances (parent substances) but also their metabolites are defined as marker residues and maximum residue limits are set as cumulative limits. For more information on the metabolism of antiparasitics and marker residues, please refer to SmPC.

The national residue control plan stipulates that around 450 samples (muscle and milk) are tested annually. In recent years, no limit values were exceeded.

Metabolism of antiparasitics and marker residues

For the majority of (pro-)benzimidazoles, not only the original drug (parent substance) but also the metabolites are defined as marker residues in Regulation (EU) 37/2010 and the maximum residue limits are set as aggregate limits.

Sample zimidazoles such as netobimin and febantel are compounds that do not contain a benzimidazole structure as such; this is only formed in the organism. Netobimin is transformed in the gastrointestinal tract to the anthelmintically active albendazole. This is then oxidized to albendazole sulfoxide (albendazole oxide or ricobendazole) and further to albendazole sulfone, which is converted to albendazole-2-aminosulfone by deacetylation of the carbamate group. Albendazole and albendazole sulfoxide are not only metabolites of netobimin, but also active ingredients of anthelmintics. For the respective cumulative limit, all subsequent substances of this metabolic series are included.

The case is similar for febantel: fenbendazole (a benzimidazole) is formed first, followed by oxfendazole (fenbendazole sulfoxide) and oxfendazole sulfone, with fenbendazole and oxfendazole also being drugs.

The metabolism of avermectins is not as rapid and pronounced. They consist in part of a mixture of different components that are not isomers but differ slightly chemically by small side groups (methyl, ethyl, hydroxy groups). For example, abamectin consists of more than 80% of the B1a component and less than 20% of the B2b component. In the case of such substance mixtures, the main components (B1a) serve as marker residues for the respective limits of Regulation (EU) 37/2010.

Substance classes

Avermectins (including milbemycins such as moxidectin), which have no antibacterial effect, have a macrocyclic lactone as a common feature in their molecular structure. They bind to glutamate-activated chloride channels typical of invertebrates such as nematodes and arthropods. This increases the membrane permeability of nerve and muscle cells, inhibiting their activity and leading to parasite death. Avermectins are metabolites of ray fungi species (Streptomyces), some of which are subsequently chemically modified. Due to the insecticidal and acaricidal effects of avermectins, one representative, abamectin, is also used as a pesticide.

Benzimidazoles are anthelmintics (worming agents) whose mechanism of action is based on binding to certain proteins of the parasite cells, the so-called tubulins. This disrupts the formation of microtubules and impairs important structural (cytoskeleton) and functional (uptake and intracellular transport of nutrients) processes in the cells, causing the worms to die and be excreted after a few days. The common feature of this class of compounds is a benzimidazole core in their molecular structure.

Levamisole is the L-isomer of tetramisole, containing equal parts of the L- and R-forms. Only the L-isomer is anthelmintically active, affecting cholinergic conduction, leading to paralysis and death of the parasite.

Spectrum of investigations and analytical methods

In the Department of Veterinary Drugs, Hormones and Contaminants of the Institute of Food Safety Vienna, we routinely analyze antiparasitics of the substance classes avermectins, benzimidazoles incl. levamisole and salicylic acid/phenol derivatives (incl. salicylanilides)/benzenesulfonamides in animal tissues and milk and are also the National Reference Laboratory for these investigations.

Regular participation in international interlaboratory comparisons and in workshops of the EU reference laboratory (EURL) in Berlin, which is responsible for antiparasitics, ensure the quality of the results and constant further development of the analytical methods to the latest state of the art and research.

The individual substance groups are each examined with their own analytical method (concerning sample preparation and measurement):

• Avermectins: analytical method: HPLC with fluorescence detection (HPLC-FLD).
• Benzimidazoles incl. levamisole: analytical method: HPLC with mass spectrometric detection (LC-MSMS) For rapid screening of avermectins and benzimidazoles incl. levamisole in milk, a chemiluminescence immunoassay is also used.
• Salicylic acid/phenol derivatives (incl. salicylanilides)/benzenesulfonamides: analytical method: HPLC with mass spectrometric detection (LC-MSMS)

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).