Liquid chromatography tandem mass spectrometry pharmacokinetic study of dl ‐praeruptorin A in rat plasma

dl ‐Praeruptorin A is a novel drug with valuable apoptosis and inflammation inhibitory effects in cardiac muscle. Previous pharmacokinetic studies of dl ‐praeruptorin A have had limited success due to its very low plasma concentrations. In this study, we developed and validated a new rapid, sensitive and specific high‐performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC/ESI–MS/MS) method for quantitative analysis of dl ‐praeruptorin A in rat plasma. dl ‐Praeruptorin A and diazepam (internal standard) extracted from rat plasma samples with chloroform and analyzed on an XTerra™ RP 18 column (150 mm × 4.6 mm i.d., 5 µm) were chromatographically separated within 5.5 min using methanol–water (75:25, v/v; flow rate 1 mL/min) as the mobile phase. dl ‐Praeruptorin A was detected in positive ion mode using multiple reaction monitoring. The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ, 2.5 ng/mL), precision (intra‐ and inter‐day <11.0%), accuracy (90.2–96.3%), recovery (>79.2%) and stability were determined. The correlation coefficient ( r 2 ) for the linear range of 2.5–2500.0 ng/mL was >0.999. No matrix effects were observed. The validated method was successfully applied to pharmacokinetic studies of dl ‐praeruptorin A after intravenous administration to rats. The LLOQ obtained with this method was lower than in previous studies and could be valuable for determination of dl ‐praeruptorin A in therapeutic drug monitoring and preclinical studies to establish appropriate dose and frequency. Copyright © 2010 John Wiley & Sons, Ltd.