Abstract: 【Objective】The aim of this study was to investigate the pharmacokinetic properties and bioavailability of tildipirosin in pigs after an intravenous or intramuscular administration of 4 mg·kg^-1 body weight. 【Method】 Twenty healthy pigs were selected and randomly divided into 2 groups and received 4 mg·kg^-1of tildipirosin injection by either intravenous or intramuscular administration. The blood was collected at 5 min, 10 min, 15 min, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d, 9 d, 10 d, 11 d, 12 d, 13 d, 14 d and 15 d after administration. Phenomenex Luna C18 (150 mm×2 mm, 5 μm) was used. Acetonitrile-0.1% formic acid aqueous solution was used as the mobile phase. The gradient elution procedure was used. The flow rate was 0.25 mL·min^-1, the column temperature was 30℃, and the injection volume was 5.0 μL. The sample was thawed naturally, 0.5 mL of plasma was accurately pipetted into a 5 mL centrifuge tube, 2 mL of acetonitrile was added, vortexed and shaken for 10 min, centrifuged at 8000 r/min for 10 min. And then the supernatant was dried with nitrogen at 35℃ and reconstituted in 1 mL of solution. 0.22 μm microporous membrane, LC-MS/MS detection analysis. Tildipirosin showed a good linearity in the concentration range of 4-1000 ng·mL^-1, with a correlation coefficient of 0.994-0.998, a detection limit of 2 ng·mL^-1, and a limit of quantification of 4 ng·mL^-1. The relative recovery rate of this method was 87.91%-104.93%, which showed a good linear relationship with the correlation coefficient of 0.994—0.998. The coefficient of intra-assay coefficient of variation was 2.12%—12.09%, and the inter-assay coefficient of variation was 3.92%—10.65%. The experimental method had high sensitivity and simple operation, and could be used for the pharmacokinetic study of tildipirosin in pigs. MS conditions of detection method: ESI ion source, positive ion scan, ion spray voltage: 5500V, TEM: 550℃, the pressure of CUR: 25 psi, the pressure of GS2 50L/min, the pressure of collision CAD: 6 psi. the quantitative ion is: tildipirosin m/z→735.1/98.0. Blood samples were collected and detected by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were estimated using the WinNonlin5.2.1 software package and SPSS 16.0 analysis of the time and concentration data.【Result】After intravenous injection, AUC_last and AUC_{inf (pred)} were (18030.30 ±7560.75) h·ng·mL^-1 and (18795.31±7455.23) h·ng·mL^-1, respectively;t_1/2 was (99.42±22.25) h, and MRT was (81.71±12.15) h. After intramuscular injection, C_max was (886.00±155.63) ng·mL^-1; T_max was (0.51 ± 0.30) h. AUC_last and AUC_{inf (pred)} were (19702.05±6442.36) h·ng·mL^-1 and (20840.08±6849.76) h·ng·mL^-1, respectively; t_1/2 was (100.83±20.23) h and MRT was (81.80±9.44) h; the absolute bioavailability was 109.27%. 【Conclusion】 After intramuscular injection, the tildipirosin was absorbed quickly in pigs, distributed widely, peaked rapidly, and eliminated slowly.

Key words: tildipirosin, pharmacokinetic, bioavailability, pig