HPLC-ESI-MS/MS validation and pharmacokinetics of kalopanaxsaponin A in rats?

RSC Advances Pub Date: 2014-12-19 DOI: 10.1039/C4RA14264K

Abstract

Kalopanaxsaponin A (KPS-A) is a potential anti-tumor active compound isolated from the stems of Stauntonia obovatifoliola Hayata subsp. intermedia. A rapid and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was firstly developed and validated for the quantification of KPS-A in rat plasma. The plasma samples were pretreated by a simple protein precipitation (PPT) procedure with methanol?:?acetonitrile (1?:?1, v/v). Chromatographic separation was successfully accomplished on an Agilent Zorbax XDB C18 column (2.1 mm × 50 mm, 3.5 μm) with a gradient elution system composed of a 0.1% formic acid aqueous solution and 0.1% formic acid in an acetonitrile solution. The flow rate was set to be 0.50 mL min?1. The multiple reaction monitoring (MRM) was based on the transitions of m/z = 749.4 → 585.5 for KPS-A and 268.9 → 158.8 for genistein (IS). The assay was validated to demonstrate the selectivity, linearity, recovery, accuracy, precision and stability. The lower limit of quantification (LLOQ) was 0.50 ng mL?1 in 25 μL of rat plasma. The developed and validated method has been successfully applied to the quantification and pharmacokinetic study of KPS-A in rats after intravenous and oral administration of KPS-A. The oral absolute bioavailability (F) of KPS-A was calculated to be 0.006 ± 0.002%, suggesting its very poor absorption and/or strong metabolism in vivo.

Graphical abstract: HPLC-ESI-MS/MS validation and pharmacokinetics of kalopanaxsaponin A in rats
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