cyadox and quinoxaline-2-carboxylic-acid

Tissue deposition and residue depletion profiles of cyadox (Cyx) and its three major metabolites, including 1,4-bisdesoxycyadox (Cy1), 4-desoxycyadox (Cy2), and quinoxaline-2-carboxylic acid (QCA), in pigs after multiple oral administrations were determined. Thirty-five healthy adult pigs were randomly divided into seven groups and orally treated with Cyx at a dosage of 20 mg/kg of body weight for five consecutive days. Each group of five pigs was randomly slaughtered 12, 24, 72, 120, 168, 216, and 264 h after the last dosing, and tissue samples, including muscle, liver, kidney, and fat, were collected and analyzed via the liquid chromatography-tandem mass spectrometry method. The concentration-time data of Cyx and its three metabolites (Cy1, Cy2, and QCA) were analyzed with WinNonlin. Results showed that metabolites of Cyx were quickly generated in swine tissues and the concentrations of QCA in kidney were higher than those of Cyx and other metabolites in all edible tissues. These results provide further insight into the metabolism of Cyx and confirmation of the residue marker and target tissue of Cyx in pigs.

Topics: Animals; Biomarkers; Biotransformation; China; Chromatography, High Pressure Liquid; Crosses, Genetic; Drug Residues; Food Additives; Food Contamination; Food Inspection; Kidney; Male; Meat; Quinoxalines; Sus scrofa; Tandem Mass Spectrometry; Tissue Distribution

Cyadox (CYX) is an antimicrobial growth-promoter of the quinoxalines. It is highly effective on improving growth and feed conversion of chicken with little toxicity. For food safety concerns, HPLC-UV methods were developed for the sequential determination of CYX and its major metabolites, 1,4-bisdesoxycyadox (BDCYX) and quinoxaline-2-carboxylic acid (QCA), in plasma, muscle, liver, kidney and fat of chicken. For CYX and BDCYX, samples were subjected to a deproteinisation, a degrease and a liquid-liquid extraction. For QCA, samples were subjected to an alkali hydrolysis, a liquid-liquid extraction and a cation exchange column (AG MP-50 resin) clean-up. Analysis was performed on a RP-C18 column by UV detection with a gradient program of wavelength. Gradient elution was performed at a flow of 1mL/min. The limits of quantification for CYX, BDCYX and QCA in plasma and tissues were 0.025microg/g, and 0.002microg/g for QCA in muscle. The recoveries of three compounds in plasma and tissues were 70-87% with inter-day relative standard deviation (R.S.D.) less than 10%. An animal experiment was performed to show the applicability of the present methods in real biological samples, which demonstrated a satisfactory applicability since all compounds could be detected nearly in all tissues. The present methods were highly sensitive and accurate, and could therefore be useful in pharmacokinetic and residue studies for cyadox in chicken. The developed methods will be further applied in the residue screening of cyadox and its metabolites in chicken.

Topics: Animals; Chickens; Chromatography, High Pressure Liquid; Fats; Kidney; Liver; Molecular Structure; Muscles; Quinoxalines; Reproducibility of Results