Simultaneous determination by LC-MS/MS of 25-methoxydammarane-3β,12β,20-triol epimers and active metabolites in rat plasma after intravenous administration

Abstract

1. The pharmacokinetics of the 25-OCH₃-PPD epimers and active metabolites in rat plasma after a single intravenous (i.v.) administration were studied by a rapid, selective and sensitive UPLC-MS/MS method.

2. Chromatographic separation was performed on an Acquity UPLC with Agela C₁₈ column, and the solvents of 5 mM ammonium acetate (pH 7.8) – acetonitrile (65: 35, v/v) were used as mobile phase for elution. The quantification was performed with the transitions of m/z 493.5 → 475.5 for 20(R,S)-25-OCH₃-PPD, m/z 479.5 → 461.5 for 20(R,S)-25-OH-PPD. The Lower Limit Of Quantitation (LLOQ) was 20.0 ng mL⁻¹ for 20(R,S)-25-OCH₃-PPD, 2.0 ng mL⁻¹ for 20(R,S)-25-OH-PPD in the plasma samples assay.

3. The pharmacokinetic parameters of AUC, t_1/2 and MRT had no difference between 20(R)- and (S)-25-OCH₃-PPD, but S-epimer has a lower plasma clearance compared to the R-isomer. The active metabolite 20(S)-25-OH-PPD showed significantly higher AUC, MRT and a longer half-life than that of 20(R)-25-OH-PPD. These assay results are necessary for the evaluation of the pharmacokinetic behavior of 25-methoxydammarane-3β,12β,20-triol in vivo.

• 25-Methoxydammarane-3β,12β
• 20-triol
• 25-OH-PPD
• active metabolite
• epimer
• pharmacokinetics
• UPLC-MS/MS