title: Simultaneous estimation of 16α-hydroxycleroda-3,13(14) Z-dien-15,16-olide from Polyalthia longifolia and its metabolite in hamster plasma: application to pharmacokinetic study.
abstract: A selective and sensitive LC-MS-MS method was developed and validated for simultaneous estimation and pharmacokinetic studies of 16α-hydroxycleroda-3,13(14) Z-dien-15,16-olide (K-09) obtained from Polyalthia longifolia and its metabolite (K-9T), a novel antidyslipidemic agent. Sample clean-up involved liquid-liquid extraction of both the analytes and internal standard (rosuvastatin) from 200 μL of hamster plasma. The analytes were chromatographically separated on a Symmetry-Shield C₁₈ (5 µm, 4.6 × 150 mm) column, using acetonitrile-0.1% aqueous formic acid (92:08, v/v) as the mobile phase. Detection was performed using negative ion electrospray ionization in multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 1.56-200 ng/mL, with a correlation coefficient (r²) of 0.998 or better. The within- and between-batch precisions (relative standard deviation, %RSD) and the accuracy (percentage bias) were within acceptable limits as per FDA guidelines. The validated method was successfully applied to reveal the pharmacokinetic parameters of K-09 and metabolite after oral administration. This method will therefore be highly useful for future studies of K-09 and metabolite K-9T pharmacokinetics in preclinical and clinical studies.
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, CSIR, Post Box 173, Lucknow 226001, India. rabi.cdri@gmail.com
authors.forename: R S
authors.initials: RS
authors.lastname: Bhatta
authors.forename: Devendra
authors.initials: D
authors.lastname: Kumar
authors.forename: Y S
authors.initials: YS
authors.lastname: Chhonker
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.forename: Suriya P
authors.initials: SP
authors.lastname: Singh
authors.forename: Koneni V
authors.initials: KV
authors.lastname: Sashidhara
authors.forename: G K
authors.initials: GK
authors.lastname: Jain
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D006224:Cricetinae; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D031044:Polyalthia; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004224:Diterpenes; C072581:16-hydroxycleroda-3,13(14)-dien-15,16-olide