Marketing authorization or registration dossiers are required to follow recommendations as described in the EMEA/CVMP/540/03-Rev1 guideline on assessing the stability of antibiotics to be administered in drinking water. However, there are currently no requirements or data available on the compatibility of disinfectants and antibiotics. This article describes the influence on the stability of 10 veterinary products in combination with 50 ppm hydrogen peroxide (H2O2) and sodium hypochlorite (0.5 ppm active chlorine) at two different concentrations (the normal concentration in drinking water, and the concentration when using a stock solution for a proportioner = 20 x normal concentration).
Materials and method
The following substances were selected for testing:
- doxycycline
- amoxicillin
- sulfadiazine / sulfadimethoxine (combined with trimethoprim)
- tiamulin
- colistin
For each substance, two formulations were chosen (Product 1 and Product 2). Two biocides were selected, being 50 ppm hydrogen peroxide and sodium hypochlorite with 0.5 ppm active chlorine (titrated and depending on pH, up to three times higher in hard water (high pH) than in soft water (low pH) to obtain 0.5 ppm active chlorine).
Two concentration levels were tested:
- Concentration of a stock solution kept in solution with a mixer for 24 hours (tested after 6 hours).
- Concentration of the treatment dosage in medicated drinking water as defined in the SPC after a period of 6 hours (1:20 dilution of the stock solution).
Stability is expressed as a percentage (%) of the remaining concentration in solution without disinfectants at the same time point.
Results
Only the results after 6 hours are shown. Typically, the results at 6 hours can be extrapolated to 24 hours.
Conclusions
- Hydrogen peroxide has a big effect on amoxicillin stability.
- Sodium hypochlorite mainly affects tiamulin and colistin activity.
- Hard water seems to decrease the stability of antibiotics more than soft water.
- Some products are less affected than others.
Practical advice
- Always use (soft) water without biocides to prepare stock solutions.
- Avoid concurrent use of biocides during treatment.
- If concurrent use of biocides cannot be avoided, use medicated solutions within 6 hours of preparation.
