一种检测促肾上腺皮质激素（1-24）的 IA-LC-MS/MS 混合方法，用于解释低剂量促肾上腺皮质激素刺激试验。

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-01 Epub Date: 2024-06-28 DOI:10.1080/17576180.2024.2360358

Barry R Jones, Junlong Shao, Mitesh Sanghvi, Alejandro Ayala, Rosa Luo, Jian Wang

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引用次数: 0

摘要

促肾上腺皮质激素 1-24（ACTH[1-24]）具有与内源性促肾上腺皮质激素（1-39）类似的作用，通过靶向肾上腺上的 MC2R 受体产生皮质醇。目前正在开发一种新的促肾上腺皮质激素受体拮抗剂，通过与 MC2R 受体结合来治疗促肾上腺皮质激素过多的疾病（如库欣病）。在一项 I 期临床研究中，使用了 ACTH(1-24) 来评估这种候选药物抑制皮质醇对 ACTH 刺激反应的能力。为支持这项研究，我们开发了一种混合免疫亲和层析色谱法，测量浓度范围为 10 至 400 pg/ml的促肾上腺皮质激素（1-24）。检测结果一致且可接受。本文将讨论测定的开发和鉴定。

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A hybrid IA-LC-MS/MS method for adrenocorticotropic hormone(1-24) to support interpretation of low-dose cosyntropin-stimulation test.

Adrenocorticotropic hormone 1-24 (ACTH[1-24]) has a similar effect as endogenous ACTH(1-39) to generate cortisol by targeting the MC2R receptor on the adrenal gland. A new investigational ACTH receptor antagonist drug is being developed to treat diseases of ACTH excess (e.g., Cushing's disease) by binding to the MC2R receptor. Administration of ACTH(1-24) was used in a Phase I clinical study to assess the ability of this drug candidate to suppress the cortisol response to ACTH stimulation. A hybrid immunoaffinity-LCMS assay measuring ACTH(1-24) with a concentration range of 10 to 400 pg/ml was developed to support the study. Consistent and acceptable A&P results were achieved. The assay development and qualification will be discussed.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.