A simple and sensitive method was developed for the simultaneous determination of four macrolides in pork using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Homogenized sample was extrac...A simple and sensitive method was developed for the simultaneous determination of four macrolides in pork using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Homogenized sample was extracted with NaH2PO4 buffer and acetonitrile solution,and defatted with n-hexane.Further cleanup was performed on a Sep-Pakt C18 solid-phase extraction cartridge.The compounds were determined by LC-MS/MS operated in positive electrospray ionization mode.The limits of detection(LODs) were 0.5 μg/kg.The average recoveries at three spiked concentration levels of 1.0,5.0,10.0 μg/kg were in the range of 70%-110%,with the intra-day RSD of less than 12.9% and inter-day RSD of less than 13.4%.展开更多
The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25...The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25, 0.5 and 1.0 mg · kg-1 of milbemycin oxime, respectively, another group received a single IV dose of 0.5 mg · kg-1. Blood samples were collected at predetermined times after drug administration and the milbemycin oxime concentrations in plasma were determined by LC-MS/MS. The drug protein binding in dog plasma in vitro was determined by equilibrium dialysis at concentrations spanning the range of values observed in vivo in dog plasma. After PO administration at doses of 0.25, 0.5 and 1.0 mg · kg-1, milbemycin oxime was slowly absorbed and eliminated, the time to reach the maximum plasma concentration(Tmax) was 4.14±0.20, 4.27±0.14 and 4.06±0.13 h, the mean absorption time(MAT) was 19.06, 13.67 and 11.77 h, the terminal rate half-life(t1/2λz) was 15.06±0.37, 11.09±0.54 and 9.76±0.89 h and the total body clearance(Cl) was 1.15±0.05, 1.18±0.03 and 1.17±0.07 m L · min-1 · kg-1, respectively. The maximum plasma concentration(Cmax, 36.50±1.40, 76.11±2.77 and 182.05±7.20 ng · m L-1, respectively) and the area under the first-moment curve(AUC-10→∞, 985.83±49.46, 1 663.12±51.42 and 3 558.04±197.88 mg · h · L, respectively) increased accordingly to the administered dose rates; the oral bioavailabilities were estimated to be 88.61%, 74.75% and 79.96%, respectively. The values of fu were 0.12%, 0.14% and 0.13% in dog plasma, respectively. In conclusion, the pharmacokinetics of milbemycin oxime in dogs following oral administration revealed its higher oral bioavailability and advantageous pharmacokinetic properties, such as its lower total body clearance and longer elimination half-life, and indicated that the single oral dose of 0.50 mg · kg-1 of milbemycin oxime which was recommended in all the parasitological efficacy studies allowed an adequate concentration of the drug.展开更多
文摘A simple and sensitive method was developed for the simultaneous determination of four macrolides in pork using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Homogenized sample was extracted with NaH2PO4 buffer and acetonitrile solution,and defatted with n-hexane.Further cleanup was performed on a Sep-Pakt C18 solid-phase extraction cartridge.The compounds were determined by LC-MS/MS operated in positive electrospray ionization mode.The limits of detection(LODs) were 0.5 μg/kg.The average recoveries at three spiked concentration levels of 1.0,5.0,10.0 μg/kg were in the range of 70%-110%,with the intra-day RSD of less than 12.9% and inter-day RSD of less than 13.4%.
基金Supported by Natural Science Fund of Heilongjiang Province(C201424)
文摘The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25, 0.5 and 1.0 mg · kg-1 of milbemycin oxime, respectively, another group received a single IV dose of 0.5 mg · kg-1. Blood samples were collected at predetermined times after drug administration and the milbemycin oxime concentrations in plasma were determined by LC-MS/MS. The drug protein binding in dog plasma in vitro was determined by equilibrium dialysis at concentrations spanning the range of values observed in vivo in dog plasma. After PO administration at doses of 0.25, 0.5 and 1.0 mg · kg-1, milbemycin oxime was slowly absorbed and eliminated, the time to reach the maximum plasma concentration(Tmax) was 4.14±0.20, 4.27±0.14 and 4.06±0.13 h, the mean absorption time(MAT) was 19.06, 13.67 and 11.77 h, the terminal rate half-life(t1/2λz) was 15.06±0.37, 11.09±0.54 and 9.76±0.89 h and the total body clearance(Cl) was 1.15±0.05, 1.18±0.03 and 1.17±0.07 m L · min-1 · kg-1, respectively. The maximum plasma concentration(Cmax, 36.50±1.40, 76.11±2.77 and 182.05±7.20 ng · m L-1, respectively) and the area under the first-moment curve(AUC-10→∞, 985.83±49.46, 1 663.12±51.42 and 3 558.04±197.88 mg · h · L, respectively) increased accordingly to the administered dose rates; the oral bioavailabilities were estimated to be 88.61%, 74.75% and 79.96%, respectively. The values of fu were 0.12%, 0.14% and 0.13% in dog plasma, respectively. In conclusion, the pharmacokinetics of milbemycin oxime in dogs following oral administration revealed its higher oral bioavailability and advantageous pharmacokinetic properties, such as its lower total body clearance and longer elimination half-life, and indicated that the single oral dose of 0.50 mg · kg-1 of milbemycin oxime which was recommended in all the parasitological efficacy studies allowed an adequate concentration of the drug.
