DETERMINATION OF THE MAJOR CIRCULATING METABOLITES OF PERILLYL ALCOHOL

紫苏醇（NSC 641066），一种天然存在的单萜，现在被 作为一种抗肿瘤药物正在接受临床前评估， 癌症研究所. 我们已经开发了一个特定的测定紫苏醇 包括将其从血浆中提取到叔丁基甲基醚中， 通过毛细管气相色谱-质谱检测。 然而，我们对小鼠的初步研究表明，紫苏醇 广泛且快速代谢;给药后任何时间 可以检测到紫苏醇。 化学品调查 给药后色谱峰组分的结构 紫苏醇揭示了主要的循环代谢物是紫苏酸 酸和二氢紫苏酸。 因此，开发一种用于 紫苏醇集中于紫苏醇的代谢物。 的 随后使用测定法研究紫苏醇（通过 其代谢物）在犬中的药代动力学。 该方法允许同时定量两种代谢物， 测定的线性动态范围从0.25 μ g/ml延伸至10 μ g/ml。

Perillyl alcohol (NSC 641066), a naturally occurring monoterpene, is now undergoing preclinical evaluation as an antitumor agent at the National Cancer Institute. We have developed a specific assay for perillyl alcohol involving its extraction from plasma into tert-butyl methyl ether followed by capillary gas chromatography with mass spectrometric detection. However, our preliminary studies in mice indicated that perillyl alcohol is extensively and rapidly metabolized; at no time post administration could perillyl alcohol be detected. Investigation of the chemical structure of chromatographic peak components following administration of perillyl alcohol revealed the major circulating metabolites to be perillic acid and dihydroperillic acid. Hence, development of an assay for perillyl alcohol has focussed on the metabolites of perillyl alcohol. The assay has subsequently been utilized to investigate perillyl alcohol (via its metabolites) pharmacokinetics in dogs. The method permits simultaneous quantitation of both metabolites with a linear dynamic range of the assay extending from 0.25 to 10 micro g/ml.