Pharmacokinetics And Residues Of Albendazole Sulfoxide In Pig

A LC-MS/MS method was developed to simultaneous determinate the concentration of Albendazole sulfoxide and Albendazole sulfone in plasma and tissues of pig. The pharmacokinetics and tissues residue depletion of Albendazole sulfoxide in pigs were also analyzed.LC-MS/MS method was used for the determination of ABZSO and ABZSO₂ in plasma and tissue samples of pigs. Electrospray ionization in the positive ion mode was used for the multi reaction monitoring detection. The parents and daughter ions of the drugs were ABZSO: m/z 282/240, ABZSO₂: m/z 298/159, phenetidin: m/z 180/110 respectively. The welchrom-C₁₈ column(4.6mm×250mm,5μm) was used for the LC, the mobile phase consisting of methanol: water (4:6, v/v) plus 1% of acetic acid, at a flow rate of 1.0mL/min.The plasma and tissue samples were prepared by liquid–liquid extraction using ethyl acetate as extracting solvent. And the tissue samples were further defatted using hexane, and improved the recovery of ABZSO and ABZSO₂ by methanol: water (8:2, v/v). Filtrated by membranes (0.2μm) before determination. The results showed that, the recoveries of ABZSO and ABZSO₂ in plasma were 90.13% and 87.32% respectively, the limit of quantitation and limit of detection were 0.0466μg/g and 0.0139μg/g respectively. The recoveries of ABZSO and ABZSO₂ in tissues were 79.31-90.04% and 83.32-93.02% respectively; the limit of quantitation were0.126-0.207μg/g and 0.084-0.113μg/g respectively, and the limit of detection were 0.038-0.062μg/g and 0.025-0.034μg/g respectively. The method which was used for the determination was proved to be suitable for the pharmacokinetic and residue depletion studies.Two different kinds of dosage form were studied for the pharmacokinetics of Albendazole sulfoxide. 6 pigs were used for each of the dosages form, Oral administration and intramuscular injection at a single dose of 10mg/kg body weight respectively. Plasma samples were collected at different time spots after administration of ABZSO. The LC-MS/MS system was used for detection after samples were extracted and cleaned. The concentration-time dates of ABZSO and ABZSO₂ in plasma were analyzed with PK Solver 1.0 program. The main pharmacokinetic parameters of ABZSO in pigs after oral administration were as follows: t1/2 7.7±2.0h, AUC 46.7±8.8μg/mL*h, Tmax 1.8±0.3 h, Cmax 5.3±0.5μg/mL, MRT 10.6±1.7h; the main pharmacokinetic parameters of ABZSO in pigs after intramuscular injection were as follows: t1/2 6.3±0.7h, AUC 26.8±2.5μg/mL*h, Tmax 8.2±3.7 h, Cmax 2.0±0.3μg/mL, MRT 9.9±1.1 h. The residue depletion of Albendazole sulfoxide was analyzed with 21 pigs. Tissue samples as liver, kidney, muscle and fat were collected at different days after administration of ABZSO, then cleaned and extracted before detection. The results verified suit for the regulations of the withdrawal periods.