Quantitation of the next-generation imipridone ONC206 in human plasma by a simple and sensitive UPLC-MS/MS assay for clinical pharmacokinetic application.


Journal

Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336

Informations de publication

Date de publication:
10 May 2022
Historique:
received: 22 10 2021
revised: 28 01 2022
accepted: 20 02 2022
pubmed: 27 2 2022
medline: 6 4 2022
entrez: 26 2 2022
Statut: ppublish

Résumé

ONC206 is an imipridone derivative that is being developed clinically as a single agent given orally in a first-in-human trial (NCT04541082). This ongoing clinical trial requires pharmacokinetic analysis of ONC206 to fully characterize its pharmacologic profile. There is currently no published bioanalytical method for ONC206 quantitation. To understand the clinical pharmacokinetics of ONC206, a sensitive yet simple uHPLC-MS/MS method for quantitation of ONC206 in human plasma was developed. Protein-precipitation allowed rapid and sensitive bioanalytical measurement of ONC206 in human plasma. A Phenomenex Kinetex C18 (50 ×2.1 mm, 1.3 µm, 100 Å) analytical column achieved symmetrical and sharp chromatography peaks of ONC206 and the internal standard, [

Identifiants

pubmed: 35219065
pii: S0731-7085(22)00106-6
doi: 10.1016/j.jpba.2022.114685
pmc: PMC8983588
mid: NIHMS1783709
pii:
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Clinical Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114685

Subventions

Organisme : Intramural NIH HHS
ID : Z01 BC010548
Pays : United States

Informations de copyright

Published by Elsevier B.V.

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Auteurs

Jennifer C Goodell (JC)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.

Sara M Zimmerman (SM)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.

Cody J Peer (CJ)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.

Varun Prabhu (V)

Chimerix, Inc, Durham, NC, USA.

Tyler Yin (T)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.

William J Richardson (WJ)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.

Arya Azinfar (A)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.

John A Dunn (JA)

Chimerix, Inc, Durham, NC, USA.

Mark Mullin (M)

Chimerix, Inc, Durham, NC, USA.

Brett J Theeler (BJ)

Department of Neurology, Uniformed Services University of the Health Sciences, USA.

Mark Gilbert (M)

Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, USA.

William D Figg (WD)

Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA. Electronic address: figgw@mail.nih.gov.

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Classifications MeSH