Simultaneous determination of aditoprim and its three major metabolites in pigs, broilers and carp tissues, and its application in tissue distribution and depletion studies

ABSTRACT

Aditoprim (ADP) is a recently developed dihydrofolate reductase inhibitor that has shown promise for therapeutic use in veterinary medicine because of its excellent pharmacokinetic properties. In this study, a sensitive and reliable multi-residue chromatography-ultraviolet (HPLC-UV) method for the quantitative analysis of ADP and its three major metabolites was developed, and the tissue distribution and depletion profiles of ADP and its major metabolites in pigs, broilers and carp were investigated. Edible and additional tissues (heart, lung, stomach, intestine and swim bladder) were collected for analysis at six different withdrawal periods after ADP administration for 7 days. ADP, N-monomethyl-ADP and N-didesmethyl-ADP were detected in almost all tissues in the three species. The liver, kidney and lung showed higher residue concentrations, and the liver showed a longer residue half-life (t_1/2) than other tissues. In the liver, ADP was the most abundant component with the longest persistence. The results suggest that the liver was the residual target tissue and ADP was the marker residue, and the conclusive withdrawal time (WDT) of 20 days in pigs, 16 days in broilers and 25 days in carp was estimated using the assessment methodologies approved by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).

Graphical Abstract

KEYWORDS:

• Aditoprim
• metabolites
• HPLC-UV
• depletion
• WDT
• dietary exposure assessment

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplemental data

Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/19440049.2016.1200751.

Additional information

Funding

This work was supported by the Risk Assessment of Unknown and Known Hazard Factors of Livestock and Poultry Products [grant number GJFP2015008].