Quantification of α- and β-amyrin in rat plasma by gas chromatography-mass spectrometry: application to preclinical pharmacokinetic study.

α- and β-Amyrins are naturally occurring triterpenes with a wide range of biological activities. In this study, a reliable GC-MS method was developed and validated for the quantification of α- and β-amyrins in rat plasma. The calibration curves were linear (R(2) > 0.996) with a limit of quantification of 1.0 ng ml(-1) for both α- and β-amyrins. The precision and repeatability of this method was good as the relative standard deviation were 12% or less. The absolute recovery ranged from 71% to 89%, while the analytical recovery ranged from 95% to 99%. The pharmacokinetic profiles of α- and β-amyrins in rats were subsequently investigated in Sprague-Dawley rats. β-Amyrin was administered intravenously and also orally in two forms, namely, as a suspension of the pure compound and the crude plant extract. α-Amyrin was administered orally as a suspension of the crude plant extract. β-Amyrin had a very long terminal elimination half-life (t(1/2λz) = 610 ± 179 min) and extremely slow clearance (Cl = 2.04 ± 0.24 ml min(-1) kg(-1)). The absolute oral bioavailability of β-amyrin in the crude plant extract was about fourfold higher than that in the suspension of pure form (3.83% vs 0.86%). When given in crude plant extract, both α- and β-amyrins had a similar dose normalized C(max). This reliable GC-MS method will enable further pharmacokinetic investigations of α- and β-amyrins.