Development and validation of a liquid chromatography–tandem mass spectrometry method for the quantification of the acetyl-coenzyme A competitive p300/CBP catalytic inhibitor A-485 in biological samples

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Abstract

The small molecule A-485 competitively inhibits the histone acetyltransferase domain of CBP (cyclic-adenosine monophosphate response element-binding protein)/p300. Apart from its antineoplastic activity, researchers are exploring its potential benefits in treating osteoporosis and its impact on energy metabolism. However, so far, only limited pharmacokinetic data are available, and the crucial determination of A-485 concentration in various biological materials with small sample volumes remains unpublished. A rapid and sensitive LC–tandem mass spectrometry method has been developed and validated to quantify A-485 in mouse serum and tissue. In this method, serum samples underwent precipitation with acetonitrile, while cell lysates were appropriately diluted. The determination of A-485 utilized a reversed-phase column with a mobile phase gradient, and detection was carried out in multiple reaction monitoring mode. The lower standard sample, with a concentration of 7.8 ng/mL, served as the lower limit of quantification, while the upper standard was established at 1000 ng/mL. A-485 concentrations were assessed in both serum samples and the lysate of all examined tissues, revealing swift metabolic clearance. The analytical method outlined here is deemed appropriate for subsequent studies. The ability to measure the active ingredient in various compartments facilitates the determination of accurate pharmacokinetic parameters. In the event of human use of A-485, the analysis method can be seamlessly transferred to human samples.

Details

OriginalspracheEnglisch
Aufsatznummere5819
FachzeitschriftBiomedical Chromatography
Jahrgang38
Ausgabenummer4
Frühes Online-Datum26 Dez. 2023
PublikationsstatusVeröffentlicht - Apr. 2024
Peer-Review-StatusJa

Externe IDs

ORCID /0000-0003-0845-6793/work/149795124
ORCID /0000-0002-5661-5376/work/149796782
ORCID /0000-0003-1526-997X/work/149798039
Scopus 85180884528
PubMed 38148286

Schlagworte

Schlagwörter

  • A-485, LC–MS/MS, protein precipitation, serum and tissue samples, Chromatography, Liquid/methods, Limit of Detection, Animals, Humans, Tandem Mass Spectrometry/methods, Antineoplastic Agents, Mice, Acetyl Coenzyme A

Bibliotheksschlagworte