| Cyadox, a new member of the quinoxalines, has good effects on commonly found pathogens in livestock and aquatic. It is highly effective on improving growth and feed conversion. Comparing to the other quinoxalines, cyadox is more efficient and less toxic to animals. As a growth promoter which used in food producing animals, its risk assessments are incomparably important for its development and application. Drug residue is the major consideration for food safety, but the metabolism and depletion of cyadox was not fully understood in the former studies. The depletion of cyadox was investigated in meat, fat, liver and kidney, but not investigated in other edible tissues, such as intestines, stomach, etc, which are particularly important in China. Based on this observation, we explored the depletion of cyadox in all edible tissues in swine, broiler and carp. A high-performance liquid chromatography method, which can detect the cyadox and its five major metabolites in heart, lung, stomach, and intestine were established. The depletion of cyadox and its metabolites in these tissues were investigated. In the present study, the results revealed that the cyadox was quickly absorbed and eliminated in swine, broiler and carp. Little parent drug and metabolites were found in the edible tissues in these animals, which indicating that the cyadox is highly safe for swine, broiler, carp and their related products. Our results here determined the target tissue and marker residue of cyadox in swine, broiler and carp, clarified its safety properties in food producing animals, and supported the risk assessment in foods from animals.1 Establish the detection methodThe present study established a multiple detection method of cyadox and its five major metabolites in liver, kidney, muscle, fat, heart, lung, stomach, large intestine and small intestine of swine and broiler and in liver, kidney, muscle, fat, skin and gastrointestinal tract of carp.The tissues were extracted by ethyl acetate, followed by a complex reagent (formic acid:methanol:acetonitrile:water, v/v 1:50:10:39), and purified by SPE method by HLB cartridge. The residue was redissolved with acetonitrile:water (v/v 15/85), and detected by the high-performance liquid chromatography at 320 nm.In this method, the quantitation limits of CyO, Cyl, and Cy6 were determined to be 15 μg/kg in muscle, heart, and lung of swine and broiler, and muscle, skin, and gastrointestinal of carp. The quantitation limits of CyO, Cyl, and Cy6 were determined to be 20Lg/kg in liver, kidney, fat, stomach and intestine of swine and broiler, and liver, kidney and fat of carp. The quantitation limits of Cy2, Cy4, and Cy9 were determined to be 20 μg/kg in muscle, heart, lung of swine and broiler, and muscle, skin, and gastrointestinal tract of carp. The quantitation limits of Cy2, Cy4, and Cy9 were determined to be 40μg/kg in liver, kidney, fat, stomach, large intestine and small intestine of swine and broiler, and liver, kidney and fat of carp. The average recovery of these compounds in tissues was more than 60%, and the withinter-day RSD was less than 12%.2 The depletion of cyadox and its metabolites in swine, broiler and carp25 healthy crossbred swines,30 twenty-day-old Kebao broiler and 30 healthy carps were divided into five groups and fed continuously administrated 200 mg/kg cyadox for 2 weeks. Animals were killed at different withdrawal time, the liver, kidney, muscle, fat, heart, lung, stomach, large intestine and small intestine were collected. The cyadox and its metabolites were quantified, and the results are shown as follows:At the withdrawal time of 6 h, CyO, Cyl, and QCA were detected in most of the swine tissues. The elimination of CyO was rapid in swine in vivo, CyO was detected in all tissues except for fat, and the concentration range of CyO was 21.8-66.3μg/kg. QCA was detected in all tissues except for fat; the concentration range of QCA was 22.4-56.9 μg/kg. Cyl have more residual but slowly elimination, and longest stay in kidney. Cy1 was detected in all tissues; the concentration range of Cyl was 20.4-66.0 μg/kg. At the withdrawal time of 1 d, CyO was eliminated to below the limit of quantitation. QCA was detected in kidney and lung, the concentration were 22.3 and 25.1μg/kg. Cy1 was detected in liver, kidney and lung, the concentration range of Cyl was 22.1-44.2μg/kg. At the withdrawal time of 3 d, QCA was eliminated to below the limit of quantitation. Cyl was detected only in kidney. At the withdrawal time of 7 d, Cyl was eliminated to below the limit of quantitation.No metabolism was detected in in broiler muscle and fat. At the withdrawal time of 6 h, CyO was detected in liver, kidney, small intestine, heart, stomach and lung, the concentration range of CyO was 21.4-67.2 μg/kg. QCA was detected in liver, kidney, small intestine, heart and lung, the concentration range of QCA was 24.7-66.7 ug/kg. Cyl was detected in liver, kidney, heart, lung, large and small intestine, the concentration of Cyl was 65.6 μg/kg in kidney. At the withdrawal time of 1 d, CyO was detected in kidney, the concentration was 34.1 μg/kg, and it was eliminated to below the limit of quantitation in other tissues. QCA was detected in kidney, the concentration was 32.5 μg/kg, and it was eliminated to below the limit of quantitation in other tissues. Cyl was detected inliver, kidney, and lung, the concentration of Cy1 was 32.0,47.4 and 23.0 μg/kg. At the withdrawal time of 3 d, CyO and QCA did not detected in all tissues. Cyl was detected in kidney. At the withdrawal time of 5 d, Cy 1 did not detected in all tissues.At the withdrawal time of 6 h, CyO, Cyl, and QCA were detected in carp tissues, and Cy4 was detected in skin and gastrointestinal. At the withdrawal time of 6 h, the concentration range of CyO was 15.2-25.5μg/kg, the concentration range of QCA was 20.2-36.1μ/kg. The concentration range of Cyl was 32.4-40.8 μg/kg. At the withdrawal time of 1 d, Cy4 did not detected in all tissues. CyO and QCA were eliminated to below the limit of quantitation in all tissues. Cyl was eliminated to below the limit of quantitation in fat. At the withdrawal time of 3 d, Cyl was detected in gastrointestinal tract. At the withdrawal time of 7 d, all tissues did not detect any metabolism.In summary, a high-performance liquid chromatography method, which can detect the cyadox and its five major metabolites in heart, lung, stomach, and intestine were established for the first time. Meanwhile, the depletion of cyadox and its metabolites in these tissues were clarified. This work would help to guide the application of the drug in clinical, and provide the basic information of safety evaluation Residues monitoring. |
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