An LC-MS/MS method for determination of the bromodomain inhibitor ZEN-3694 and its metabolite ZEN-3791 in human plasma

We have developed and validated a novel LC-MS/MS method for the simultaneous quantification of ZEN-3694 and its active metabolite ZEN-3791 in human plasma after protein precipitation. Stable isotope-labeled versions were used as internal standards. Chromatographic separation was achieved on a Kinetex C18 column using 0.1% formic acid in H2O and 0.1% formic acid in MeOH as mobile phases. Detection was performed via positive electrospray ionization mode with multiple reaction monitoring. The assay exhibited linearity in the concentration range of 5-5000 ng/ml for both analytes. Intra- and inter-assay precision and accuracy were within ±11%. ZEN-3694 and ZEN-3791 recoveries were between 93 and 105%. This LC-MS/MS assay is an essential tool to study ZEN-3694 in an ongoing clinical trial (NCT04840589).

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Bioanalysis - (2024) vom: 18. März

Sprache:

Englisch

Beteiligte Personen:

Feng, Ye [VerfasserIn]
Mahdi, Haider [VerfasserIn]
Piekarz, Richard [VerfasserIn]
Beumer, Jan H [VerfasserIn]
Synold, Timothy W [VerfasserIn]

Links:

Volltext

Themen:

Assay
BET bromodomain inhibitor
Chromatography
Clinical
Journal Article
LC–MS
Mass spectrometry
ZEN-3694
ZEN-3791

Anmerkungen:

Date Revised 18.03.2024

published: Print-Electronic

ClinicalTrials.gov: NCT04840589

Citation Status Publisher

doi:

10.4155/bio-2023-0252

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369873963