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

[ Vol. 13 , Issue. 5 ]

Author(s):

Xun-Yu Xiong, Hong-Jiang Yu and Ye-Fei Nan   Pages 452 - 461 ( 10 )

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.

Affiliation:

College of Chemistry and Chemical Engineering, Xi’an Shiyou University, Xi'an 710065, College of Chemistry and Chemical Engineering, Xi’an Shiyou University, Xi'an 710065, College of Chemistry and Chemical Engineering, Xi’an Shiyou University, Xi'an 710065

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