A sensitive liquid chromatography–mass spectrometry method for simultaneous determination of three diterpenoid esters from Euphorbia lathyris L. in rat plasma

A selective and sensitive liquid chromatography–mass spectrometry (LC–MS) method was developed for the simultaneous determination of Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 from Euphorbiae semen in rat plasma. Larotaxel was added to a 200 μL plasma sample as the internal standard (IS). The plasma sample was extracted by 2 mL ether and separated on an Elite C18 column (150 mm × 4.6 mm, 5 μm) with the mobile phase of methanol–water performing gradient elution within 11.0 min. All the three analytes were detected in the selected ion monitoring (SIM) mode with positive electrospray ionization. The calibration curves were linear in the range of 2.0–200 ng/mL and the lower limits of quantification (LLOQ) were 2.0 ng/mL for all the three analytes. The intra-day and inter-day precisions were all within 8.6% and 14.6% for the three analytes, while the accuracy was less than 9.7% and 7.5%, respectively. The validated method was firstly and successfully applied to the pharmacokinetic study of Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 from Euphorbiae semen after oral administration in rat plasma.