LC-MS/MS法研究左旋去甲基苯环壬酯在比格犬体内的生物利用度

目的评价左旋去甲基苯环壬酯在比格犬体内生物利用度。方法 LC-MS/MS法测定比格犬口服和静脉给药后体内的血药浓度,计算药代动力学参数和绝对生物利用度。结果比格犬口服给药2 mg/kg后5 min即可测得血中药物含量,口服给药后1 h左旋去甲基苯环壬酯在比格犬体内血药浓度达峰,给药后36 h血中药物浓度均已降至LLOQ以下。比格犬口服和静脉注射2 mg/kg左旋去甲基苯环壬酯的t1/2分别为(5.36±0.82)h和(6.73±2.00)h,Cmax分别为(141.88±51.03)和(591.84±144.61)μg/L;AUC(0-36 h)分别为(962.42±220.96)和(1572.06±365.80)μg.L-1.h;用AUC(0-36 h)计算比格犬口服单剂量左旋去甲基苯环壬酯的绝对生物利用度为(61.22±10.78)%。结论左旋去甲基苯环壬酯口服给药吸收迅速,绝对生物利用度较高,具有良好的开发前景。

Determination of levodesmethylphencynonate hydrochloride by LC-MS/MS and its bioavailability in Beagle dog

Objective To evaluate the bioavailability of levodesmethylphencynonate hydrochloride in Beagle dogs after an oral dose.Methods An LC-MS/MS method was used for determining the plasma concentration of levodesmethylphencynonate in Beagle dogs after intravenous injection or oral administration at the equivalent dose.The pharmacokinetic parameters and absolute bioavailability of the two groups were calculated.Results After an oral dose,levodesmethylphencynonate was detected at the first time point(5 min).The mean maximum plasma level(Cmax) of 141.88 μg/L was reached at the 1 h.The plasma concentration was below the LLOQ at 36 h post-dosing.Main pharmacokinetic parameters of oral dose group and intravenous injection(iv) group were as follows: t1/2:(5.36±0.82) and(6.73±2.00)h,Cmax:(141.88±51.03) and(591.84±144.61)μg/L;AUC(0-36 h):(962.42±220.96) and(1572.06±365.80)μg·L-1·h.The absolute bioavailability of levodesmethylphencynonate hydrochloride was(61.22±10.78)%.Conclusion The results showed that the compound is quickly absorbed with a highly oral absolute bioavailability.