Pharmacokinetics And Residue Depletion Of Quinocetone In Carp

Quinocetone,a new antibacterial growth promotant of quinoxalines,is used as medicinal feed additive and antibacterial growth promoters for swine and chicken. Quinocetone has been indicated as safe and effective compound as growth promoter. Aquiculture is an important food industry.Quinocetone can promote growth rate,improve the survive ratio and water quality,so it has great potential to be used in aquaculture.This study was designed to develop analytical methods for quinocetone and its two main metabolites,desoxyquinocetone(DQCT) and 3-methylquinoxaline-2-carbo xylic acid (MQCA),in carp(Cyprinus carpio L.) plasma and tissues,and then investigation of pharmacokinetics and residues depletion of quinocetone in carp(Cyprinus carpio L.) were investigated.The marker residue and target tissue were determined,and a withdrawal time of quinocetone for carp(Cyprinus carpio L.) was estimated.These results would provide safe approval information of quinocetone for fish use.In this study,analysis methods of quinocetone and its two main metabolites(DQCT and MQCA) in plasma and tissue had been developed.The accuracy,precision,detection limit and relative standard deviation had also been investigated.The results had shown that LOQ of all three chemicals were 8μg/L in blood,and the precision and relative standard deviation were satisfied with the requirements of analysis method.The LOQ of quinocetone(QCT) and desoxyquinocetone(DQCT) was 4μg/kg in muscle,10μg/kg in skin,and 20μg/kg in liver,respectively.By using the national standard of MQCA for reference,the LOQ of MQCA in muscle,skin and liver was 4μg/kg,10μg/kg and 10μg/kg, respectively.Precision and relative standard deviation was also satisfied with the requirements of analysis method.To investigate the pharmacokinetics of quinocetone in carp(Cyprinus carpio L.) plasma,320 carp Cyprinus carpio L.(averaging 450±50 g in weight) were divided into two groups,single dose of QCT(2.5mg/kg b.w.) administered byⅣand oral administration(200mg/kg b.w.).The blood was drawn after at different time intervals. After pretreating the plasma samples,the HPLC was used to determine the concentrations. The results had shown:when carps(Cyprinus carpio L.) were administrated with quinocetone intravenously at a single dose of 2.5mg/kg b.w.,only QCT was detected.The concentration versus time was fitted with open two compartments.The T1/2αand T1/2βwere 0.32h and 11.33h,respetively.The AUC was 9.65(μg/mL)·h,which indicated that QCT could be distributed rapidly and deleted slowly in carp(Cyprinus carpio L.).When carps(Cyprinus carpio L.) were administrated with quinocetone orally at a single dose of 200mg/kg b.w.,the concentration versus time was fitted with open one compartment.The T1/2αand T1/2e were 2.53 h and 9.90h,respectively.The AUC was 1.72(μg/mL).h,C_max was 0.08μg/mL and the bioavailability was 0.23%,which indicated that quinocetone could be absorbed and eliminated slowly with low bioavailability.To investigate the residues of QCT,190 carp(Cyprinus carpio L.) were fed with 75mg/kg QCT in diet for consecutive 12 weeks.After 12 week,10 fishes were randomly assigned to different predetermined time intervals of 4h,12h,24h,2,3,5,7,10,14,21, 28,35 days.Then HPLC methods were used to determine the concentrations of quinocetone and its two main metabolites in muscle,skin and liver.The results showed that:The concentrations of QCT in muscle,skin and liver were below LOQ after a withdraw time of 72h,4h and 48h,respectively,and below the LOD after a withdraw time of 5d,12h and 72h,respectively.The concentrations of DQCT in muscle,skin and liver were below LOQ after a withdraw time of 48h,24h and 12h,respectively,and below the LOD after a withdraw time of 5d in muscle and skin and 72h in liver.The concentrations of MQCA in muscle,skin and liver were below MRL after a withdraw time of 7d,12h and 10d,respectively,and below the LOD after a withdraw time of 10d,7d and 21d, respectively.These results had shown that:the t_1/2 of MQCA in liver was the most persistant compared with QCT and its main metabolites in all edible tissues.Therefore liver was designated as the target tissues and MQCA was designated as the marker residue of QCT in carp(Cyprinus carpio L.).The concentration of MQCA was 0.045μg/g in liver after a withdraw time of 4h,but below the LOD after a withdraw time of 21d.The elimination half-time t_1/2β was 3.56d.So far,no MRL of MQCA was established in fish, based on the toxicology results,a temporary MRL of 1.8μg/g was established.Since the concentration of MQCA in liver after a withdrawal period of 4h was much lower than 1.8μg/g,it can be concluded that no withdraw time was needed for QCT in fish.The analyzing method,in this study,exhibits that sensitivity was high,periods of detect was short and the cost was low.At the same time,it can also provide the reference of examining the other quinoxalines drug in animals.In this study,the pharmacokinetic and residue depletion of QCT in carp(Cyprinus carpio L.) firstly investigated,a withdrawal time of quinocetone for carp(Cyprinus carpio L.) in feed was determined,and analytical methods of quinocetone and its two main metabolites in edible tissue developed,these results will provide science gist for the safety evaluation and right use for QCT in carp(Cyprinus carpio L.),furtherty improve the healthy development of aquaculture and food safety.