Pharmacokinetic Study of Corynoline and Acetylcorynoline in LPS-Induced Acute Lung Injury Rats After Oral Administration ofCorydalis Bungeana Turcz Extract

OBJECTIVE To explore the pharmacokinetics of corynoline and acetylcorynoline in LPS induced acute lung injury（ALI） rats after oral administration ofCorydalis bungeana Turcz extract. METHODS LC-MS/MS analytical method was developed and fully validated to determine corynoline and acetylcorynoline in rat plasma. Plasma samples were prepared by acetonitrile precipitation and then separated in a C₁₈ column. The analytes were determined in an ESI source and then by MRM mode. The method was then fully validated by specificity， linearity， precision， accuracy， matrix effect， recovery and stability. Then， a comparative pharmacokinetic study of corynoline and acetylcorynoline in normal and LPS induced acute lung injury rats was performed， following the oral administration ofCorydalis bungeana Turcz extract (428 mg/kg). The plasma samples were then collected and analyzed after oral administration of the extract. Pharmacokinetic parameters were then calculated by the DAS3.0. RESULTS Calibration curves indicated that a desirable linearity (R²>0.995) were found and the linearity range for corynoline was 0.25-100.0 ng/mL， and 0.40-160.0 ng/mL for acetylcorynoline. And the LLOQs were sufficient for quantitative analysis. The precision and accuracy were assessed by intra-batch and inter-batch assays， and the relative standard deviation (RSD) and the accuracy (RE) was all acceptable. The extraction recoveries， matrix effects and stability were also acceptable in this study. The pharmacokinetic study indicated that the AUC_(0-t) of corynoline in ALI rats was significantly increased when comparing with control rats. But the systemic exposure of acetylcorynoline was not changed in ALI rats as compared with the normal rats. CONCLUSION The developed LC-MS/MS method is fast， sensitive， accuracy and can be used in the pharmacokinetic study of corynoline and acetylcorynoline after oral administration ofCorydalis bungeana Turcz extract in rats. And the exposure of corynoline was significantly increased， while the clearance was significantly decreased in the ALI rats as compared with the control rats.