trans-2,6-Difluoro-4'-N,N-dimethylaminostilbene (DFS), a synthetic stilbene, displayed potent pre-clinical anti-cancer activities exceeding that observed for naturally occurring resveratrol. In this study, a simple and sensitive HPLC method was developed and validated to quantify DFS in rat plasma. The lower limit of quantification (LLOQ) was 5ng/ml. The intra- and inter-day variation in terms of relative standard deviation (RSD) was all less than 10%. The bias rate ranged from -11.5% to 6.2% while the absolute recovery ranged from 94.1±2.3 to 97.3±4.4%. The pharmacokinetic profiles of DFS were examined in Sprague-Dawley rats after intravenous administration (2 mg/kg). DFS displayed moderate clearance (Cl=61.5±17.7ml/min/kg) and a relatively prolonged terminal elimination half-life (t1/2 λz) of 351±180min. Aqueous solubility played a crucial role in the oral absorption of DFS. When DFS was given as a suspension (6mg/kg), the absolute oral bioavailability (F) was almost negligible. However, when DFS was given in a solution prepared with hydroxypropyl-β-cyclodextrin (6mg/kg), the F was 12.4±10.7%. Dose-escalation to 15mg/kg resulted in much higher systemic exposure (F=40.2±10.0%). As DFS is orally available after formulation with hydroxypropyl-β-cyclodextrin and pharmacologically active systemic concentrations could be achieved after a single oral dose, the use of DFS as a cancer chemopreventive/chemotherapeutic agent is possible.
|Number of pages||6|
|Journal||Journal of Pharmaceutical and Biomedical Analysis|
|State||Published - Jan 18 2013|
Bibliographical noteFunding Information:
The work of Hai-Shu Lin was supported by a start-up grant from the National University of Singapore and a research grant from the National University of Singapore Academy of GxP Excellence . The work of Paul C. Ho was supported by a research grant from the National University of Singapore ( R-148-000-104-112 ). The work of Chunming Liu was supported by a research grant ( CA139359 ) from the National Institutes of Health (USA) .
- Absolute oral bioavailability
ASJC Scopus subject areas
- Analytical Chemistry
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry