Oral and i.v. pharmacokinetics of isosteviol in rats as assessed by a new sensitive LC-MS/MS method
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A sensitive liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed to investigate isosteviol pharmacokinetics in vivo. Isosteviol was extracted from plasma with hexane and 4% formic acid. A Phenomenex Synergi 2堆usion reversed phase analytical HPLC column (50 mm נ2.0 mm) equipped with a Synergi 2堆usion guard column was employed for chromatographic separations. The gradient mobile phase consisted of acetonitrile (ACN) and 20 mM ammonium acetate at pH 6.5, starting at 20% ACN and ramping to 80% at 7 min, followed by 80% ACN for 1 min, then 20% ACN for 5 min. Negative SRM was used to monitor the m/z 317.1/317.1 and 317.3/317.3 transitions for isosteviol and 395.0/395.0 and 397.0/397.0 transitions for internal standard. The retention time of isosteviol was 9.2 min. The assay was linear over the range of 50-2000 ng/mL. The accuracy of the method was in the range of 97-105%. Intra- and inter-day precisions were in the range of 1.5-4.6%. Isosteviol (4 mg/kg) was dosed intravenously and orally to Sprague-Dawley rats (n = 6). Plasma samples were collected and analysed. Intravenous isosteviol has a distribution half-life of 35.7 ᠹ.0 min with the initial distribution volume of 68.1 ᠹ.4 mL. The total clearance, terminal half-life and steady-state volume of distribution were 1.25 ᠰ.12 mL/min, 150.6 ᠵ0.5 min and 272.6 ᠹ5.9 mL, respectively. The oral bioavailability of isosteviol was found to be 60.4 ᠱ5.5%.
Journal of Pharmaceutical and Biomedical Analysis