Preliminary Study On Pharmacokinetics And Residue Of Cefquinome Sulphate In Pigs

Cefquinome ( CEF ) is the first fourth - generation used only for veterinary cephalosporin, and shows a broad spectrum antimicrobial activity. A method to detect cefquinome in pig plasma and tissues by high performance liquid chromatorgraphic (HPLC) with ultra violet detector was developed to analysis the pharmacokinetics index and residue of cefquinome in pigs in this paper.1 The detemination of Cefquinome by HPLCA method for the determination of Cefquinome by HPLC was established. The HPLC system consisted of C₁₈ column (4.6 mm×150 mm,5μm),the mobile phase was 3.45 g perchlorate in 1000 mL water-phosphates 12 mL (adjust pH to 3.6 with triethlamine): Acetonitrile (90:10), the flow rate was 0.8 mL·min^-1,and the detection wavelength was 270 nm,injection volume was 20μL and column temperature was 30℃.The calibration curve was linear in the range of 0.06 mg·mL^-1-0.14 mg·mL^-1, regression formula were obtained through determination with HPLC method: A = 42382 C-162477 (r=0.9999), the limit of detection was 0.005μg·mL^-1,the RSD of the variation coefficient was 0.43 % within a run or 0.53 % between runs, respectively. The RSD of repetition rate was 0.93%. The RSD of stability within eight hours was 0.86%. The result showed that the method was rapid, simple and accuratefor the content determination of Cefquinome, the content of cefquinome in test solution is 99.3% compared with signed content (2.5%). The result accorded with the regulation of vaterinary drug quality criterion.2 The detemination of four residual solvents in Cefquinome sulphate byGas chromatographyA Gas chromatography method was developed to determine ethanol, acetone, dichloromethane and toluene those four resiodual solvents in cefquinome sulphate. DB-624 quartz capillary column was used. The temperature programming was as follows: the initial temperature was kept at 40℃for 10 min, then raised to 220℃at the rate of 30℃·min^-1 and keep for 10 min, the injector temprature was 220℃and detector temprature was 230℃,flow rate:5 mL·min^-1,split ratio:50:1.The result showed that there was a good linearity (r=0.9994-0.9998) between peak area and concentration. The detection limit of ethanol, acetone, dichloromethane and toluene were 1.67μg·mL^-1,1.89μg·mL^-1,2.56μg·mL^-1,2.02μg·mL^-1 (S/N=5), the average recovery of the preparation were 97.69%-99.42%, the RSD were all below of 5% (n =3).This method is simple, acurate, reproducible and suitable for quality control of cefquinome suulphate, the result accorded with the regulation of vaterinary drug quality criterion..3 Preliminary studies on the Pharmacokinetics of Cefquinome in pigsSPE-HPLC method to be established to determine of cefquinome in swine plasma. Cefquinome sulphate were administrated intramuscularly at a dose of 2 mg·kg^-1·b.w to six swine. After extracted with methanol, cefquinome concentration of preparation samples were determined by HPLC/UV with solid phase extraction method.C₁₈ was used as the revesed column, sodium perchlorate-phosphoric acid buffer( pH 3.6):acetonitrile( 90:10 V/V) as the mobile phate, the concentration-time date were analyzed with 3p97 computer program. In present studies, the standard curves for cefquinome was linar in a range of 0.05-25μg·mL^-1,r=0.9993, the detect limit was 0.05μg·mL^-1.Adding 0.5, 5,and 25μg·mL^-1 cefquinome into blank plasma,the recovery rate were (90.67±0.84 )%, ( 94.06±1.26 )%, and( 91.64±2.03 )%, respectively, and the coefficient of variation was 0.94%, 0.63%, and 1.96% within a run or 0.48%, 1.28%, and 2.22% between runs, respectively. The results suggested that the kinetics of the injection is fit to two compartment model with first order absorption. The main parameters of cefquinome was T_1/2α:(0.67±0.11)h,T_1/2β: (2.28±0.49)h,T_1/2Ka:(0.40±0.12 )h,CL/F(s):( 0.27±0.03 )L·kg^-1·h,V/F (c):(0.40±0.10 )μg±mL^-1,T_max:(0.80±0.05)h,C_max:(2.44±0.24)μg·mL^-1,AUC: (7.28±1.11)μg·mL^-1·h.We concluded that cefquinome been absorbed rapidly, long persistence effective time.There's enough effect after 18 h by intramuscularly cefquinome,a dosage of 2 mg·kg^-1 and 1 day 1 time was recommended.4 Preliminary studies on the residues of Cefquinome in swine tissuesResidues of cefquinome ( CEF ) was investigated in 24 healthy pigs following five days intramuscular administration of the drug at the dosage of 2 mg·kg^-1.Tissue samples includding muscle, liver, kidneys, lung and skin+fat were collected at different intervals after last administration. The concentration of CEF were determined by HPLC method. The method permitted a limit of detection of 20μg·kg^-1, and the concentration of cefquinome in all tissues were well lined within 20μg·kg^-1-500μg·kg^-1.Three concentration levels(20μg·kg^-1,100μg·kg^-1,500μg·kg^-1) of cefquinome in the blank tissues were analysed. The recovery of all samples were all exceed 78%,and the average recovery of muscle, liver, kidneys, lung and skin+fat was 81.57%,82.42%,81.29%,83.97%,78.80%, respectively.The intra-day coefficient of variation were between 1.82% and 6.25%. The inter-day coefficient of variation were between 1.11% and 6.35%. The result showed that the concentration of cefquinome in lung, skin+fat was declined to lower than LOD level at the 4 d, and that in others tissues was declined lower than LOD at the 5d. Accodding to the MRLs standards and the study result, a 3-day of withdrawal time was recommended.