羟氯喹亚麻酸酯在Beagle犬的药代动力学
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摘要
目的研究羟氯喹亚麻酸酯(AHQ)在Beagle犬体内的吸收行为特征以及在体内转化为羟氯喹的转化率。方法色谱柱:ASB C_(18)(50 mm×2. 1 mm,3μm),流动相为乙腈-0. 5%甲酸水溶液=55∶45,流速:0. 4 mL·min~(-1),进样量:50μL。6只Beagle,雌雄各半,单剂量静脉推注AHQ 3 mg·kg~(-1),采集血浆样本,用液相-串联质谱法测定血药浓度,用Win6. 2计算药代动力参数。结果 AHQ的主要药代动力学参数如下。t_(1/2)为(1. 5±0. 3) h,C_(max)为(1026. 0±149. 6)μg·mL~(-1),AUC_(0-t)为(639. 0±134. 6)μg·mL~(-1)·h,AUC_(0-inf)为(665. 0±142. 7)μg·mL~(-1)·h。结论 AHQ在Beagle犬体内具有快速消除的特点。
Objective To study the absorption behavior of acid ester of hydroxychloroquine and linolenic acid( AHQ) in Beagle dogs and the conversion rate of AHQ into hydroxychloroquine. Methods Chromatographic column C_(18)( 50 mm × 2. 1 mm,3 μm) with the mobile phase is acetonitrile-0. 5% formate aqueous solution = 55 ∶ 45 at a flow rate of 0. 4 mL·min~(-1). Single dose intravenous injection of 3 mg·kg~(-1) AHQ was performed in 6 Beagle dogs,each male and female. The injection volume was 50 μL. After intravenous injection of Beagle dogs,plasma samples collected and it were measured by liquid phase-tandem mass spectrometry. The pharmacokinetic parameters were calculated by Win6. 2 software. Results The pharmacokinetic parameters were as follows: t_(1/2) was( 1. 5 ± 0. 3) h,C_(max)was( 1026. 0 ± 149. 6) μg·mL~(-1),AUC_(0-t)was( 639. 0 ± 134. 6) μg·mL~(-1)·h,AUC_(0-inf)was( 665. 0 ± 142. 7) μg·mL~(-1)·h. Conclusion AHQ shows fast elimination characteristics.
Objective To study the absorption behavior of acid ester of hydroxychloroquine and linolenic acid( AHQ) in Beagle dogs and the conversion rate of AHQ into hydroxychloroquine. Methods Chromatographic column C_(18)( 50 mm × 2. 1 mm,3 μm) with the mobile phase is acetonitrile-0. 5% formate aqueous solution = 55 ∶ 45 at a flow rate of 0. 4 mL·min~(-1). Single dose intravenous injection of 3 mg·kg~(-1) AHQ was performed in 6 Beagle dogs,each male and female. The injection volume was 50 μL. After intravenous injection of Beagle dogs,plasma samples collected and it were measured by liquid phase-tandem mass spectrometry. The pharmacokinetic parameters were calculated by Win6. 2 software. Results The pharmacokinetic parameters were as follows: t_(1/2) was( 1. 5 ± 0. 3) h,C_(max)was( 1026. 0 ± 149. 6) μg·mL~(-1),AUC_(0-t)was( 639. 0 ± 134. 6) μg·mL~(-1)·h,AUC_(0-inf)was( 665. 0 ± 142. 7) μg·mL~(-1)·h. Conclusion AHQ shows fast elimination characteristics.
引文
[1]肖洪涛,童荣生,廖治,等.羟氯喹亚麻酸酯及其合成方法:中国,ZL 2013 1 0744461. 5[P]. 2016-03-30.
[2]张朴,魏敏吉,孔申申.头孢硫脒在Beagle犬的药代动力学[J].中国临床药理学杂志,2018,34(2):161-164.
[3]胡楠,鲁晓雨,赵娣,等. LC-MS/MS法测定大鼠血浆中硝苯地平及其代谢物氧化硝苯地平的浓度[J].中国临床药理学杂志,2017,33(23):2420-2423.
[2]张朴,魏敏吉,孔申申.头孢硫脒在Beagle犬的药代动力学[J].中国临床药理学杂志,2018,34(2):161-164.
[3]胡楠,鲁晓雨,赵娣,等. LC-MS/MS法测定大鼠血浆中硝苯地平及其代谢物氧化硝苯地平的浓度[J].中国临床药理学杂志,2017,33(23):2420-2423.