Perillyl alcohol (POH), a metabolite of d-limonene and a component of the lavender oil, is currently in Phase I clinical trials both as a chemopreventative and chemotherapeutic agent. In vivo, POH is metabolized to less active perillic acid (PA) and cis- and trans-dihydroperillic acids [DHPA, 4-(1'-methylethenyl)-cyclohexane-1-carboxylic acid]. Previous pharmacokinetic studies using a GC-MS method detected POH metabolites but not POH itself; thus these studies lacked information on the parent drug. The present report describes a sensitive GC-MS method for the quantitation of POH and metabolites using stable-isotopically labeled internal standards. The residue obtained from CH2Cl2 extraction of a plasma sample was silylated. The products were separated on a capillary column and analyzed by an ion-trap GC-MS using NH3 chemical ionization. POH-d3 was used as the internal standard for POH while 13C-PA-d2 was used as the internal standards for the metabolites. The quantitation limits for POH, PA, cis- and trans-DPA were <10 ng/ml using 1-2 ml plasma. The assay was validated in rat and human plasma. The assay was linear from 2 to 2000 ng/ml for POH, 10 to 1000 ng/ml for PA and trans-DHPA, and 20 to 1000 ng/ml for cis-DHPA monitored. The within-run and between-run coefficients of variation were all <8

作者：Z, Zhang；H, Chen；K K, Chan；T, Budd；R, Ganapathi

来源：Journal of chromatography. B, Biomedical sciences and applications 1999 年 728卷 1期