Detection of ionophores in animal tissues

Felipe Reggeti, Nick Schrier, David MacKay

Animal Health Laboratory, University of Guelph, Guelph, ON (Reggeti, Schrier), Agriculture and Food Laboratory, University of Guelph, Guelph, ON (MacKay)

AHL Newsletter 2023;27(1):10.

Ionophores are antibiotics approved as feed additives for certain species due to effective anticoccidial properties, as well as enhancement of feed efficiency and rate of weight gain.  These drugs are safe when used according to label specifications; however, when the dose exceeds the recommendations (e.g., feed mill mixing errors) or the medicated feed is inadvertently consumed by off-target species, high morbidity and mortality may occur.

The diagnosis of ionophore toxicosis is based upon history of exposure, identification of compatible clinical signs and histopathological lesions, and quantitative analysis of feed (dose) and gastrointestinal (GI) contents (exposure).  On occasions, the level of exposure is unknown, the available feed samples are not representative, and GI contents are not collected during postmortem examinations; therefore, testing fresh tissues provides the only opportunity for further assessment.  The main limitations with this approach are that ionophores are rapidly excreted from the body, and detailed information on pharmacokinetics for interpretation of the significance of tissue levels is limited.  As a consequence, estimation of the ingested dose by extrapolation from tissue levels is difficult, if at all possible, and unfortunately, not practical.  Thus, the main objective of testing tissues for ionophores should be to confirm exposure.

Detection of ionophores in tissues is particularly helpful when investigating incidents involving non-target/susceptible species (e.g., horses), because any residues in biological specimens would be considered significant.  In a series of cases looking at the diagnostic value of monensin concentration in tissue from horses following toxicosis, exposure was confirmed by toxicological analysis of serum, urine, blood, liver, heart and stomach content; however, there was no correlation between tissue concentrations and clinical outcome. 

The Agriculture and Food Laboratory (AFL) at the University of Guelph offers analytical testing of selected antimicrobials in animal tissues for regulatory monitoring.  The “Veterinary Drug Screen” (LC-MS/MS) is a multi-target analysis (MTA) that includes the ionophores monensin, narasin, lasalocid and salinomycin, as well as other antibiotics and non-ionophore anticoccidial drugs (Table 1). The high sensitivity of the test makes it suitable for food safety analysis, but it can also be used in cases of suspected toxicosis.  Samples for toxicological investigations may be submitted through the Animal Health Laboratory (AHL).  The method is validated for fresh/frozen liver (poultry) and kidney (ruminants and swine), as well as skeletal muscle (all species).  For questions, please contact the AHL Toxicology laboratory: ahltoxi@uoguelph.ca.   AHL

Table 1. Veterinary Drug Screen listing compounds detected with minimum quantification limits (MQL)

References

1. Hall JO. Ionophores. In: Plumlee’s Clinical Veterinary Toxicology. Plumlee, KH, ed. Mosby, 2004:120-127.

2. Puschner B, et al. Serum, milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation. J Vet Pharmacol Ther 2016;39(4):363-372.

3. Bautista AC, et al. Diagnostic value of tissue monensin concentrations in horses following toxicosis. J Vet Diagn Invest 2014;26(3):423-427.