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™ RP₁₈ column (150 mm x 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 (r²) 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.
Department of Pharmaceutical Science, College of Medical, Xiamen University, Xiamen, 168 Daxue Road, Xiamen 361005, China.
Hang
H
Ruan
Zhen
Z
Zhang
Xuan
X
Zhu
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003374:Coumarins / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D003374:Coumarins; C441070:praeruptorin A