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

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis 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

引用次数: 0

Abstract

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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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。

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.