首页> 外文期刊>Asian journal of drug metabolism and pharmacokinetics >Pharmacokinetics of 3-hydroxyandrost-5-en-17-one succinate (A1998) after intravenous injection in rabbits by HPLC with precolumn derivatization
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Pharmacokinetics of 3-hydroxyandrost-5-en-17-one succinate (A1998) after intravenous injection in rabbits by HPLC with precolumn derivatization

机译:柱前衍生化高效液相色谱法在兔体内静脉注射3-羟基雄蕊5-en-17-一琥珀酸酯(A1998)的药代动力学

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Aim To investigate the pharmacokinetics of 3-hydroxyandrost5-en-17-one succinate (A1998) in rabbits.Methods The plasma concentration - time courses of A1998 were measured by the method of precolumn derivatization HPLC in rabbits after intravenous administration of A1998 and the pharmacokinetic parameters were calculated by program 3p97 software. Results: The method of precolumn derivatization HPLC for determination of plasma concentration of A1998 was established by means of two C-17 carbonyls in molecule A1998 were derived by 2,4-dinitrophenylhydrazine (2,4-DNPH) becoming a double hydrazones, which greatly enhanced the detecting sensitivity of A1998. The linearity of standard curves of A1998 in range of 0.05-10mugcentre notmL~(-1) was excellent (r=0.9998); the relative recoveries of A1998 from plasma was more than 90%; the inter-day and intra-day precision (RSD) were lower than 15% and the lowest detection concentration (LOQ)was 50 ngcentre notmL~(-1). The results indicated that the plasma concentration-time courses of A1998 were best fitted to two-compartment open models after intravenous injection of 3 doses (10, 20 and 30 mgcentre notkg~(-1), respectively). The major pharmacokinetic parameters of A1998 were as following: t_(1/2beta)0.36+-0.06 h, 2.67+-0.58 h and 2.36+-2.87 h ; Vc 4.40+-0.57, 6.11+-1.36 and 5.39+-2.40 Lcentre notkg~(-1) and AUC 1.13+-0.24, 4.46+-0.97 and 6.14+-1.91mugcentre notml~(-1)centre noth~(-1), respectively. Conclusion The results indicated that A1998 was distributed and eliminated rapidly from rabbit plasma. The plasma concentrations of A1998 was increased as dose-dependent manner in the range of 10-30 mgcentre notkg~(-1), and the elimination of A1998 from plasma coincided with first order kinetics in rabbits.
机译:目的探讨3-羟基雄酮5-en-17-1琥珀酸酯(A1998)在家兔体内的药代动力学。方法采用柱前衍生HPLC法测定家兔静脉注射A1998后血浆中A1998的血药浓度-时间变化及药代动力学。参数由程序3p97软件计算。结果:建立了柱前衍生HPLC测定A1998血浆浓度的方法,是通过将分子A1998中的两个C-17羰基衍生为2,4-二硝基苯肼(2,4-DNPH)成为双而衍生的。增强了A1998的检测灵敏度。 A1998的标准曲线在0.05-10mug·centmL〜(-1)范围内线性良好(r = 0.9998);血浆中A1998的相对回收率超过90%。日间和日内精度(RSD)均低于15%,最低检测浓度(LOQ)为50 ngcentremL /(-1)。结果表明,静脉内注射3剂(分别为10、20和30 mgcentnotkg〜(-1))后,A1998的血浆浓度-时间进程最适合于两室开放模型。 A1998的主要药代动力学参数如下:t_(1 / 2beta)0.36 + -0.06h,2.67 + -0.58h和2.36 + -2.87h; Vc 4.40 + -0.57、6.11 + -1.36和5.39 + -2.40 Lcentre notkg〜(-1)和AUC 1.13 + -0.24、4.46 + -0.97和6.14 + -1.91ugcentre notml〜(-1)中心noth〜(- 1)。结论结果表明A1998在兔血浆中迅速分布并消除。 A1998的血浆浓度以剂量依赖性的方式增加,在10-30 mgcentnotkg〜(-1)的范围内,并且从血浆中消除A1998与兔子的一级动力学相吻合。

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