Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
J Pharm Biomed Anal. 2018 Apr 15;152:289-297. doi: 10.1016/j.jpba.2018.01.044. Epub 2018 Jan 31.
Cladrin, an isoflavone is a major bioactive constituent found in stem bark of Butea monosperma with remarkable osteogenic activity. A speedy and sensitive UPLC coupled tandem mass spectrometry (UPLC-MS/MS) method was developed, validated and successfully applied to bioavailability, blood partitioning, plasma protein binding, intravenous and multiple-dose oral pharmacokinetics of cladrin in rats. Separation was done on C18 column (5.0 μm, 4.6 × 50 mm) using mobile phase containing acetonitrile and 0.10% formic acid in the ratio of 65:35 (v/v) with 0.60 mL/min flow rate. The method was highly sensitive and has a short run time of 2.50 min with an excellent linearity (R > 0.99) in the range of 0.20-200 μg/L. Absolute bioavailability was found to be 16.58, 19.04 and 6.76% at oral doses of 5, 10, and 20 mg/Kg, respectively. Cladrin was rapidly absorbed (T 3.0 h) with a high apparent volume of distribution (15.03 ± 1.79L/Kg), high clearance (2.27 ± 0.30L/h/Kg) and high plasma protein binding. The present study is a first comprehensive in-vitro as well as the in-vivo preclinical pharmacokinetic report of cladrin giving insights about its drug-likeness and further development as a potential therapeutic agent.
紫檀芪是一种异黄酮，是补骨脂素中主要的生物活性成分，具有显著的成骨活性。本研究建立并验证了一种灵敏、快速的超高效液相色谱-串联质谱法（UPLC-MS/MS），并成功应用于紫檀芪在大鼠体内的生物利用度、血分配、血浆蛋白结合、静脉注射和多次口服药代动力学研究。采用 C18 柱（5.0μm，4.6×50mm），以乙腈和 0.10%甲酸的体积比为 65:35（v/v）的混合溶液作为流动相，流速为 0.60mL/min，实现紫檀芪的分离。该方法灵敏度高，运行时间短（2.50min），在 0.20-200μg/L 范围内具有极好的线性（R＞0.99）。口服 5、10 和 20mg/Kg 剂量的紫檀芪后，绝对生物利用度分别为 16.58%、19.04%和 6.76%。紫檀芪吸收迅速（T 3.0h），表观分布容积（15.03±1.79L/Kg）高，清除率（2.27±0.30L/h/Kg）高，血浆蛋白结合率高。本研究首次全面报道了紫檀芪的体外和体内临床前药代动力学特征，为其药物特性和进一步开发为潜在治疗药物提供了依据。
