Please use this identifier to cite or link to this item: https://doi.org/10.3390/molecules19079577
Title: Quantification of the resveratrol analogs trans-2,3-dimethoxystilbene and trans-3,4-dimethoxystilbene in rat plasma: Application to pre-clinical pharmacokinetic studies
Authors: Ng, S.Y
Cardullo, N
Yeo, S.C.M
Spatafora, C
Tringali, C
Ong, P.-S 
Lin, H.-S 
Keywords: 3,4-dimethoxystilbene
resveratrol
stilbene derivative
animal
bioavailability
chemistry
drug screening
drug stability
high performance liquid chromatography
liver microsome
male
metabolism
rat
reproducibility
Animals
Biological Availability
Chromatography, High Pressure Liquid
Drug Evaluation, Preclinical
Drug Stability
Male
Microsomes, Liver
Rats
Reproducibility of Results
Stilbenes
Issue Date: 2014
Publisher: MDPI AG
Citation: Ng, S.Y, Cardullo, N, Yeo, S.C.M, Spatafora, C, Tringali, C, Ong, P.-S, Lin, H.-S (2014). Quantification of the resveratrol analogs trans-2,3-dimethoxystilbene and trans-3,4-dimethoxystilbene in rat plasma: Application to pre-clinical pharmacokinetic studies. Molecules 19 (7) : 9577-9590. ScholarBank@NUS Repository. https://doi.org/10.3390/molecules19079577
Abstract: trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'- Trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through a 12.5-min gradient delivery of a mixture of acetonitrile and water at the flow rate of 1.5 mL/min at 50 °C. The lower limit of quantification was 10 ng/mL. After successful validation, the pharmacokinetic profiles of 2,3-DMS and 3,4-DMS were subsequently studied in Sprague-Dawley rats. Upon single intravenous administration (4 mg/kg), 2,3-DMS had a medium volume of distribution of the central compartment (Vc = 2.71 ± 0.51 L/kg), quite rapid clearance (Cl = 52.0 ± 7.0 mL/min/kg), moderate mean transit time (MTT0?last= 131.0 ± 4.5 min) but a fairly long terminal elimination half-life (t1/2 ?Z= 288.9 ± 92.9 min). Interestingly, 3,4-DMS displayed a pharmacokinetic profile apparently distinct from 2,3-DMS and it had more extensive distribution (Vc = 5.58 ± 1.73 L/kg), faster clearance (Cl = 143.4 ± 40.5 mL/min/kg) and shorter residence (MTT0?last = 61.4 ± 27.1 min). Following single oral administration (10 mg/kg), 2,3-DMS had low and erratic plasma exposure (Cmax = 37.5 ± 23.7 ng/mL) and poor oral bioavailability (2.22% ± 2.13%) while the oral bioavailability of 3,4-DMS was even poorer than 2,3-DMS. Clearly, the location of the methoxy groups had a significant impact on the pharmacokinetics of resveratrol analogs. This study provided useful information for the design of resveratrol derivatives in future study.
Source Title: Molecules
URI: https://scholarbank.nus.edu.sg/handle/10635/175319
ISSN: 1420-3049
DOI: 10.3390/molecules19079577
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