A Highly Sensitive Chemiluminescence Method and Application in Rapid Pharmacokinetic Study of Matrine in Rat Plasma

Background: Pharmacokinetic study plays important role in evaluating of the druggability of investigational drugs and clinical monitoring of marketed drugs. Methods: This work developed a sensitive chemiluminescence (CL) method for rapidly studying drug pharmacokinetics in rats using matrine as a probe. The method involved a flow-injection CL (FI-CL) technique that enables matrine to inhibit a luminol/sulfobutylether-beta-cyclodextrin (SBE-beta-CD)- CL reaction system. Results: A good linear relationship was found between the inhibition of CL intensity and the logarithm of matrine concentration over the range of 0.28 ng/ml to 560.0 ng/ml with a detection limit of 0.1 ng/ml (3 sigma). The maximum drug plasma concentration (C-max), time to C-max, absorption half-life (t(1/2 alpha)) elimination half-life (t(1/2 beta)), and areas under the plasma concentration-time curve AUC((0-t)) and AUC((0-infinity)) were determined to be 48.29 +/- 2.45 mu g/ml, 0.083 +/- 0.006 h, 0.079 +/- 0.005 h, 0.079 +/- 0.03 h, 23.79 +/- 1.16 mu g/h.ml and 30.51 +/- 0.82 mu g/h.ml when the rats were administrated matrine by intravenous injection through tail. The values of t(1/2 alpha), t(1/2 beta), AUC((0-t)) and AUC((0-infinity)) changed to 0.073 +/- 0.005 h, 0.82 +/- 0.03 h, 32.03 +/- 1.31 mu g/h.ml and 35.24 +/- 0.92 mu g/h.ml when the dosed matrine was replaced by SBE-beta-CD/matrine inclusion. The pharmacokinetic profile of matrine was in accordance with an open two-compartment model after administration of matrine alone or SBE-beta-CD/matrine inclusion. These results indicated that SBE-beta-CD inclusion sustained the release of matrine, prolonged the matrine distribution from the blood to the tissues and improved its bioavailability. Conclusions: The proposed method has potential to become a powerful alternative for rapid pharmacokinetic studies due to the advantages of a good linear range, high sensitivity, high recovery and superior analytical efficiency.