DETERMINATION OF THE MAJOR CIRCULATING METABOLITES OF PERILLYL ALCOHOL

紫苏醇(NSC 641066)是一种天然存在的单萜烯，现在是 作为一种抗肿瘤药物在国家医疗中心进行临床前评估 癌症研究所。我们开发了一种测定紫苏醇的特殊方法。 将其从血浆中提取到叔丁基甲醚中，然后 采用毛细管气相色谱-质谱法进行检测。 然而，我们在小鼠身上的初步研究表明，紫苏醇 被广泛而快速地代谢；在服药后的任何时候 能检测到紫苏醇吗。对该化学品的调查 给药后色谱峰成分的结构 紫苏醇显示主要的循环代谢物是紫苏醇 酸和二氢紫苏酸。因此，建立了一种新的检测方法 紫苏醇主要研究紫苏醇的代谢物。这个 随后利用化验方法研究紫苏醇(通过 其代谢物)在狗体内的药代动力学。 该方法允许同时定量这两种代谢物 测定的线性范围为0.25~10微克/毫升。

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.