High-performance liquid chromatographic and pharmacokinetic analyses of an intravenous submicron emulsion of perillyl alcohol in rats.
Perillyl alcohol (POH) is currently in phase II clinical trials both as a chemopreventative and chemotherapeutic agent. The present report describes a simple, rapid and sensitive HPLC-UV method to quantify POH in rat plasma. After protein precipitation with acetonitrile, POH was separated using an Agilent Zorbax XDB C(18) column (150 mm x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile-water (40:60, v/v) at a flow rate of 1.0 ml min(-1), and detected at 210 nm. The method has been used successfully to determine trace levels of POH in plasma down to 0.015 microg ml(-1). The pharmacokinetics of POH after intravenous administrations in three formulations, i.e. POH solution (POH-SOL), negatively charged submicron emulsions (POH-SE) and positively charged submicron emulsions (POH-CSSE) were investigated. AUC(0-infinity), MRT, t(1/2alpha) and t(1/2beta) of POH-SE and POH-CSSE were significantly higher, while their total body clearance was lower than those of POH-SOL. In addition, AUC(0-infinity), MRT and t(1/2beta) of POH-CSSE were significantly higher than those of POH-SE. The results indicate that the submicron emulsion formulation significantly increases POH blood concentrations and retention within the systemic circulation.
Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan Province 450052, PR China. hhylu@yahoo.com.cn
Hai-Ying
HY
Hua
Yong-Xing
YX
Zhao
Lin
L
Liu
Qi-Xia
QX
Ye
Shi-Wen
SW
Ge
D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004333:Drug Administration Routes; D004355:Drug Stability; D004655:Emulsions; D006207:Half-Life; D039821:Monoterpenes / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013047:Specific Pathogen-Free Organisms; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
D004655:Emulsions; D039821:Monoterpenes; C032208:perillyl alcohol