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.
Hua
Hai-Ying
HY
Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan Province 450052, PR China. hhylu@yahoo.com.cn
Zhao
Yong-Xing
YX
Liu
Lin
L
Ye
Qi-Xia
QX
Ge
Shi-Wen
SW
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