Synthesis of Stable Isotope-Labeled Steroids as Internal Standards

作为内标的稳定同位素标记类固醇的合成

• 批准号: 7584972
• 金额: $ 9.87万
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2008-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7584972
• 关键词: Synthesis; Stable; Isotope; Labeled; Steroids

Our goal is to regiospecifically synthesize stable-isotope labeled steroids for use in liquid chromatography-mass spectroscopy (LC-MS) assays for endogenous steroid hormones such estrogens, androgens, and progestogens that are believed to play critical roles in various cancers (such as breast, endometrial, ovarian and prostate). The long term goal of this work is to develop synthetic methodology for estrone, estradiol and progesterone derivatives that is both reproducible, and that gives high purity isotopically labeled steroids with the isotopes incorporated at non-exchangeable positions. The research in this proposal is designed to verify our methodology by examining various synthetic alternatives in order to meet the criteria of a reproducible synthesis, placement of the stable isotope labels at non-exchangeable positions such that the steroids are labeled to at least M+3, in a good to high yielding overall process. The long term goal is to scale up the chemical syntheses of these stable isotope-labeled steroids and combine them in one or more kits. These stable isotope standards will permit academic and clinical laboratories to establish sensitive, accurate LC-MS method~ for measuring endogenous steroid hormones in biologic samples and to standardize the measurements across laboratories.

我们的目标是特异性地合成稳定同位素标记的类固醇，用于液-质联用(LC-MS)分析内源性类固醇激素，如雌激素、雄激素和孕激素，这些激素被认为在各种癌症(如乳腺癌、子宫内膜癌、卵巢癌和前列腺癌)中起关键作用。这项工作的长期目标是开发雌酮、雌二醇和孕酮衍生物的合成方法，该方法既可重现，又能得到高纯度的同位素标记的类固醇，其中的同位素包含在不可交换的位置。 本提案中的研究旨在通过检查各种合成替代品来验证我们的方法，以满足可重复合成的标准，将稳定的同位素标记放置在不可交换的位置，以便在良好到高产率的整个过程中将类固醇标记到至少M+3。 长期目标是扩大这些稳定的同位素标记类固醇的化学合成，并将它们组合在一个或多个试剂盒中。这些稳定的同位素标准将允许学术和临床实验室建立灵敏、准确的LC-MS方法来测量生物样品中的内源性类固醇激素，并使实验室之间的测量标准化。