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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

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

Author(s): Xun-Yu Xiong*, Hong-Jiang Yu and Ye-Fei Nan

Volume 13, Issue 5, 2017

Page: [452 - 461] Pages: 10

DOI: 10.2174/1573412913666161110111715

Price: $65

Abstract

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-β-cyclodextrin (SBE-β-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 (3ó). The maximum drug plasma concentration (Cmax), time to Cmax, absorption half-life (t1/2α), elimination half-life (t1/2β), and areas under the plasma concentration-time curve AUC(0-t) and AUC(0-∞) were determined to be 48.29±2.45 µg/ml, 0.083±0.006 h, 0.079±0.005 h, 0.079±0.03 h, 23.79±1.16 µg/h•ml and 30.51±0.82 µg/h•ml when the rats were administrated matrine by intravenous injection through tail. The values of (t1/2α), t1/2β, AUC(0-t) and AUC(0-∞) changed to 0.073±0.005 h, 0.82±0.03 h, 32.03±1.31 µg/h•ml and 35.24±0.92 µg/h•ml when the dosed matrine was replaced by SBE-β- CD/matrine inclusion. The pharmacokinetic profile of matrine was in accordance with an open twocompartment model after administration of matrine alone or SBE-β-CD/matrine inclusion. These results indicated that SBE-β-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.

Keywords: Luminol, chemiluminescence, matrine, SBE-β-CD, pharmacokinetics, FI-CL.

Graphical Abstract

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