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

Autor: Jones BR; Crinetics Pharmaceuticals, 6055 Lusk Blvd, San Diego, CA 92121, USA., Shao J; Pharmaron (Germantown) Lab Services, Inc., 20340 Seneca Meadows Parkway, Germantown, MD 20876, USA., Sanghvi M; Pharmaron (Germantown) Lab Services, Inc., 20340 Seneca Meadows Parkway, Germantown, MD 20876, USA., Ayala A; Crinetics Pharmaceuticals, 6055 Lusk Blvd, San Diego, CA 92121, USA., Luo R; Crinetics Pharmaceuticals, 6055 Lusk Blvd, San Diego, CA 92121, USA., Wang J; Crinetics Pharmaceuticals, 6055 Lusk Blvd, San Diego, CA 92121, USA.
Jazyk: angličtina
Zdroj: Bioanalysis [Bioanalysis] 2024; Vol. 16 (14), pp. 711-720. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1080/17576180.2024.2360358
Abstrakt: 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.
Databáze: MEDLINE