Abstract:
:Pinostilbene (3-methoxyresveratrol or trans-3,4'-dihydroxy-5-methoxystilbene) is a naturally occurring monomethylether analogue of resveratrol (trans-3,5,4'-trihydroxystilbene) that exhibits various pharmacological activities. To further examine its medicinal potential, a sensitive LC-MS/MS method was developed and validated for the determination of pinostilbene in rat plasma. Heavy Isotope labelled resveratrol was used as an internal standard. The ESI was operated in its negative ion mode while pinostilbene and resveratrol were measured by multiple reaction monitoring (MRM) using precursor-to-product ion transitions of m/z 241→181 and m/z 233→191, respectively. This LC-MS/MS method had excellent selectivity, sensitivity (LLOQ=1ng/ml), accuracy (both intra- and interday analytical recovery within 100±15%) and precision (both intra- and interday RSD < 15%). The matrix effect was insignificant. The pharmacokinetics of pinostilbene was subsequently profiled in Sprague-Dawley rats. Upon intravenous administration (5 or 10mg/kg), pinostilbene displayed rapid clearance (Cl=129±42 or 107±31ml/min/kg) and extremely short mean transit time (MTT=6.24±0.41 or 8.52±1.38min). After oral dosing (50mg/kg), the bioavailability of pinostilbene was limited but highly erratic (F=1.87±2.67%). Pharmacokinetic comparison among pinostilbene, resveratrol and some resveratrol analogues suggested that stilbenes with meta-hydroxyl group(s) may be associated with metabolic instability and subsequently suffer from rapid clearance and low oral bioavailability. The information obtained from this study will facilitate further exploration on pinostilbene as well as other resveratrol analogues.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Chen W,Yeo SC,Chuang XF,Lin HSdoi
10.1016/j.jpba.2015.12.051subject
Has Abstractpub_date
2016-02-20 00:00:00pages
316-21eissn
0731-7085issn
1873-264Xpii
S0731-7085(15)30314-9journal_volume
120pub_type
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