Pharmacokinetic study of eight coumarins of Radix Angelicae Dahuricae in rats by gas chromatography–mass spectrometry

Abstract

A sensitive, specific gas chromatography–mass spectrometry (GC–MS) method was established for the quantitative determination of eight coumarins of Radix Angelicae Dahuricae including coumarin, isopsoralen, psoralen, xanthotoxin, bergapten, osthole, imperatorin and oxypeucedanin in rat plasma. Nitrendipine was used as the internal standard (IS). The plasma samples were extracted by acetonitrile. GC separation was accomplished on a DB-5MS column with temperature programmed from 160°C (17min) to 190°C (10min) at the rate of 20°C/min, then to 240°C (5min) at 20°C/min, and finally to 280°C (14min) at 20°C/min. The detection was performed on a quadrupole mass spectrometer detector operated by full-scan mode (m/z 50–500). The lower limit of quantitation was 5–10ng/mL for eight coumarins, and the linear range was 5–1000ng/mL for the coumarins (R2>0.9990). All the validation data were within the required limits. After oral administration, the plasma concentration–time curves showed that the time for maximum concentration (Tmax) was 1.29 for coumarin, 1.83 for isopsoralen, 1.93 for psoralen, 1.30 for xanthotoxin, 2.04 for bergapten, 0.64 for osthole, 1.41 for imperatorin and 0.51h for oxypeucedanin. The plasma concentration of the eight coumarins was low, with a mean maximum plasma concentration (Cmax) <6.41μg/mL. Pharmacokinetic data analysis showed that the eight coumarins had different pharmacokinetic characteristics after oral administration. The method was successfully applied to pharmacokinetic studies of eight coumarins after oral administration in rats.