Development and validation of UPLC-MS/MS assay for quantification of cladrin: Absolute bioavailability and dose proportionality study in rats.
J Pharm Biomed Anal
; 152: 289-297, 2018 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-29454264
ABSTRACT
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⯵m, 4.6â¯×â¯50â¯mm) using mobile phase containing acetonitrile and 0.10% formic acid in the ratio of 6535 (v/v) with 0.60â¯mL/min flow rate. The method was highly sensitive and has a short run time of 2.50â¯min with an excellent linearity (R2â¯>â¯0.99) in the range of 0.20-200⯵g/L. Absolute bioavailability was found to be 16.58, 19.04 and 6.76% at oral doses of 5, 10, and 20â¯mg/Kg, respectively. Cladrin was rapidly absorbed (Tmax 3.0â¯h) with a high apparent volume of distribution (15.03⯱â¯1.79L/Kg), high clearance (2.27⯱â¯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.
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MEDLINE
Assunto principal:
Bioensaio
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Cromatografia Líquida de Alta Pressão
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Espectrometria de Massas em Tandem
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Isoflavonas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article