Studies On The Pharmacokinetics And Residual Elimination Of Praziquantel In Grass Carp

Praziquantel（PZQ）as an anti-parasitic drug is exclusively used to treat tapeworm and trematode infections in humans and animals.Up to now,only Japan has established the maximum residue limit（MRL）for praziquantel in aquatic products.In this study,the pharmacokinetics and residue elimination of praziquantel in grass carp were carried out,which could provide the theoretical basis for the establishment of the MRL and withdrawal period for praziquantel in grass carp.A LC-MS/MS method was developed for the determination of praziquantel and its main metabolite 4-hydroxypraziquantel in grass carp plasma and meat（meat+skin）.The results showed that the matrix-matched standard curves for praziquantel,trans-4-hydroxypraziquantel and cis-4-hydroxypraziquantel were good linearity with correlation coefficients higher than 0.99 in the range of 1.00～100 ng/m L.At three spiked concentration levels of 1.00,10.0 and 100 ng/m L（ng/g）,the average recoveries of three analytes in fish plasma and meat were in the range of 82.9%～119.8%and 97.5%～114.8%,respectively,with the relative standard deviation less than 16%.The limits of quantifications（LOQs）of analytes in fish plasma and meat were 1.0 ng/m L and 1.0 ng/g,respectively.The pharmacokinetics and residue elimination of praziquantel and4-hydroxypraziquantel in grass carp were investigated.The grass carp was orally administered praziquantel at a single dose of 10 mg/kg b.w..The results showed that the praziquantel was absorbed rapidly in grass carp.The Tmax and Cmax of praziquantel in plasma were 1 h and 2394.9 ng/m L,respectively.The T_max of both trans-4-hydroxypraziquantel and cis-4-hydroxypraziquantel was 8 h,and the C_max were440.2 ng/m L and 226.9 ng/m L,respectively.According to the instructions of praziquantel premix（for aquatic products）,the praziquantel was administered to grass carp at 2 mg/kg b.w.by mixed-feeding,once every 3 days,and the elimination of residue of praziquantel in grass carp was investigated after three times of continuous administration.The C_max（43.5ng/g）of praziquantel in fish meat was found after 12 h drug withdrawal.The praziquantel was eliminated rapidly,and could not be detected after 120 h drug withdrawal.The concent of metabolite 4-hydroxypraziquantel in fish meat was nearly 10 times lower than that of the prototype drug praziquantel.The C_max of trans-4-hydroxypraziquantel（5.2 ng/g）and cis-4-hydroxypraziquantel（4.7 ng/g）were found at 12 h.The elimination rate of cis-4-hydroxypraziquantel was the fastest,and its content in fish was below the LOQ,and trans-4-hydroxypraziquantel was not detected out at 120 h.According to the toxicological data of praziquantel in the literature,the NOAEL of praziquantel was 33 mg/kg b.w.,and thus the ADI calculated was 0.17 mg/kg b.w.Based on the results of pharmacokinetics and residue elimination in grass carp,it is considered that it is not necessary to establish a MRL for praziquantel in aquatic products,but the recommended the withdrawal time is 95 degree days.