title: Quantification of α- and β-amyrin in rat plasma by gas chromatography-mass spectrometry: application to preclinical pharmacokinetic study.
abstract: 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.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Ching
authors.forename: Hai-Shu
authors.initials: HS
authors.lastname: Lin
authors.forename: Chay-Hoon
authors.initials: CH
authors.lastname: Tan
authors.forename: Hwee-Ling
authors.initials: HL
authors.lastname: Koh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D010936:Plant Extracts; D009828:Oleanolic Acid; C036380:beta-amyrin