Study On The Residue Elimination Of Tildipirosin In Pigs

Tildipirosin, a derivative of tylosin, is one of the latest semisynthetic macrolide antibiotics specifically for us on animals, which was produced by Intervet International BV. Tildipirosin is used to prevent and treat the respiratory diseases caused by susceptibal bacterias in swine and cattle. It can provide a complete treatment after single intramuscular or hypodermic administration. The trade name of its sterile injection is Zuprevo. European Medicine Agency(EMA) for Veterinary Medicine had accepted the market license agreement application of Zuprevo on March 8, 2011, and then permitted sales in the countries of Europe.Reports on residue depletion of tildipirosin in food-producing animals were relatively less. In our study, high-performance liquid chromatography- tandem mass spectrometry(HPLC-MS/MS) method was developed to determine the concentration of tildipirosin in porcine tissues.The residue elimination of tildipirosin was studied in edibility tissues of pig.The results were to provide experimental basis for developing withdrawal time of tildipirosin injection after intramuscular administration in pigs.The condition of HPLC-MS/MS was optimized using C18 analytical chromatographic column with acetonitrile and 0.1% formic acid solution as mobile phase in the gradient elution. The calibration curves of tildipirosin were linear in the concentration range of 2.5?g/kg~250?g/kg, with correlation coefficients were more than 0.996. The limit of detection( LOD) and quantification(LOQ) of the method for tildipirosin were 1.25?g/kg and 2.5?g/kg, respectively for all matrices,and the recoveries were in the range of 66.3%~97.2% with RSDs of 1.0%~14.3% at 2.5?25?250?g/kg while blank samples were spiked with tildipirosin. This analytical method met the requirement for the assay.In order to study the residue elimination of tildipirosin,30 healthy pigs were randomly allocated to six treatment groups. Another two pigs were remained untreated as controls. All of the treatment groups were administered at the dosseage of 4 mg/kg body weight. Six treatded pigs were slaughtered at 6, 24, 72, 144, 216 and 336 h after intramuscular- administration.Injection site,muscle, fat, liver and kidney tissues were sampled and analyzed by HPLC-MS/MS.The results showed that the elimination of tildipirosin was slow after intramuscular administration(4 mg/kg b.w..). The duration time of tildipirosin residual concentration in pig tissues was as follow: injection site> liver> kidney> adipose> muscle.Except at the injection site,the residue concentration in kidney is highest,the residue time is longist,therefore,it suggests that kidney can be treated as a target tissue for monitoring testosterone tildipirosin in swine. EMA for Veterinary Medicine provides the maximum residue limits about muscle? fat? liver?kidney of pig, with the responding values were respectively 7500?g/kg, 800?g/kg, 1200?g/kg, 10000?g/kg and 5000?g/kg,and the report of “Committee for Medicinal Products for Veterinary Use” recommend the maximum residue limits about the injection site was 7500?g/kg. According to the regulation, the withdrawal time of tildipirosin injecfion in pigs was calculated by WT1.4 software.The results showed that the withdrawal time of tildipirosin injection in injection site tissue?kidney?liver?adipose? muscle was respentively 9.3days?7.8 days?7.0days? 4.2days and 0days respentively.the results showed that the withdrawal time of tildipirosin(4%) in pigs was 10 days after intramuscular administration(4 mg/kg b.w..) of tildipirosin injection.