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.

Clerodane Diterpenoids Identified from Polyalthia longifolia Showing Antifungal Activity against Plant Pathogens

“…11,12 Of the clerodane diterpenoids identified in this study, compound 6 was most abundantly present in the active fraction of the P. longifolia extract and highly active against several plant pathogenic fungi and bacteria. In previous studies, compound 6 has been reported as a chemotaxonomic marker exhibiting a wide range of biological and pharmaceutical activities, including as caterpillar antifeedant 9 and antileishmanial, 10 anticancer, 36 antidyslipidemic, 37 antihyperlipidemic, 37 and antimicrobial activities. 38,39 For the initial structure− activity relationship study, the γ-hydroxyl group at C-16 of 6 was acetylated in this study, and we found that the acetate analogue (6a) lost its antifungal activities (Table 2).…”

A rapid and sensitive LC-MS/MS analysis of diapocynin in rat plasma to investigate in vitro and in vivo pharmacokinetics

“…The liquid chromatography mass spectrometer (LC-MS/MS) provides a useful separation and detection technique for the determination of drug in biological matrices with enviable accuracy, sensitivity, selectivity, robustness and shorter run time. [13][14][15] To support the pharmacokinetic and metabolism study of diapocynin, an accurate, rapid and reproducible bioanalytical method was essential. To the best of our knowledge, pharmacokinetic characteristics of diapocynin have been unexplored.…”