Studies On Pharmacokinetics Of Tildipirosin Injection In Pigs

Tildipirosin(Tildipirosin, TIP) is a new semi-synthetic antimicrobial drugs belongs to the family of Macrolides. TIP is a broad-spectrum and high-efficiency antimicrobial agents. It has activity against the pathogene of respiratory disease, including Actinobacillus pleuropneumoniae, Haemophilus parasuis, Pasteurella multocida, Bordetella bronchiseptica, Mannheimia haemolytica, Histophilus somni, etc. TIP is one of the best drugs for the treatment of respiratory disease. TIP is a new veterinary drug, but not onsale in the Chinese drug market presently. In this study, we established the LC-MS/MS and the internal standard test method. Furthermore, we finished this study on the pharmacokinetics of the Tildipirosin injection in pigs.MS conditions of detection method : ESI ion source, positive ion scan, ion spray voltage: 5.5 k V, TEM: 600℃, the pressure of CUR: 20 psi, the pressure of GAS1 and GAS2: 35 psi and 40 psi, the pressure of collision CAD: 9 psi. the quantitative ion is: m/zâ†'735.1/98.0(Tildipirosin), m/zâ†'917.6/174.4(Tylosin). The chromatographic conditions: SB-C18(2.1×150 mm, 3.5μm)HPLC column, mobile phase: acetonitrile- 0.1% formic acid in water, gradient elution with 0 min(10:90), 1 min(10:90), 6 min(60:40), 6.4 min(95:5), 12 min(95:5), 12.1 min(10:90), 18 min(10:90), flow rate:250 μL/min, the column temperature was 20℃, the injection volume was 10 μL. The plasma samples were extracted with acetonitrile, using the mixed standard method, N2 blow-dry, and dissolution by mobile phase. The TIP rendered in the 0.005-0.8 μg/m L concentration within a good linear relationship, the coefficient of association(R2) is 0.9994. The LOD and the LOQ were 0.002 μg/m L and 0.005 μg/m L, and the recoveries of different concentrations were 86.96%-95.52%, the Intra-day precision and Inter-day variable coefficient were controlled under 15%. The TIP at room temperature,-80℃ long-term freezing and thawing conditions showed that this method was stable and corresponded with the biological sample analysis requirements. The result showed that this method was sensitive, simple, and it can be used in the pharmacokinetic study of Tildipirosin.Pharmacokinetics experimental results showed that: plasma Pharmacokinetic parameters were determined using noncompartmental analysis via DAS 3.0(Bio Guider Co., Shanghai, China). The main pharmacokinetic parameters after im 2, 4, 8 mg/kg bw TIP injection were as follow, Cmax: 0.475±0.114, 0.972±0.391, 0.987±0.164 μg/m L; Tmax: 0.208±0.165, 0.389±0.18, 0.236±0.153 h; t1/2: 118.69±33.78, 124.45±42.06, 82.73±23.69 h; AUC: 11.04±1.27, 15.75±5.19, 37.54±4.83 μg/m L*h. This experiment data provides a theoretical basis for clinical rational drug use of Tildipirosin injection.