title: LC-ESI-MS/MS method for bioanalytical determination of osteogenic phytoalexin, medicarpin, and its application to preliminary pharmacokinetic studies in rats.
abstract: Medicarpin is the active phytoalexin found in the stem bark of Butea monosperma having potent osteogenic activity. An LC-ESI-MS/MS was developed and validated for quantification of medicarpin in rat plasma using liquid-liquid extraction technique and diethyl ether as the extraction solvent. Medicarpin was separated on RP18 column (4.6mm×50mm, 5.0μm) using methanol and 10mM ammonium acetate (pH 4.0) in the ratio of 80:20 (v/v) as mobile phase. The method was linear within the concentration range of 1-500ng/mL and its sensitivity was 1ng/mL. The precision value for intra- and inter-day assays and stability assays was within 0.88-14.22% while the accuracy ranged between 87.46-116.0% at all four QC levels. The validated method was successfully applied to study the preclinical pharmacokinetics of medicarpin in rats. Medicarpin showed multiple peak phenomenon upon oral administration. Its oral bioavailability was 17.43%. It was found to be a rapidly absorbed (Tmax=15min), 81.61% protein bound and pH stable compound. The present study provides important information regarding preliminary pharmacokinetics of medicarpin for its further exploration as a potential therapeutic agent.
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Isha
authors.initials: I
authors.lastname: Taneja
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Kanumuri Siva Rama
authors.initials: KS
authors.lastname: Raju
authors.affiliation: National Institute of Pharmaceutical Education and Research, Raebareli, Uttar Pradesh, India.
authors.forename: Muralikrishna
authors.initials: M
authors.lastname: Challagundla
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Raghuvanshi
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Goel
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India. Electronic address: wahajuddin@cdri.res.in.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wahajuddin
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D011485:Protein Binding; D036343:Pterocarpans / Q000032:analysis* / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000032:analysis* / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000094162:Phytoalexins
chemical_list: D036343:Pterocarpans; D012717:Sesquiterpenes; C047353:medicarpin; D000094162:Phytoalexins
keywords: Bioanalytical method validation; Bioavailability; Extraction; LC–MS/MS; Pharmacokinetics; Recovery