Quantification of Linrodostat and its metabolites: Overcoming bioanalytical challenges in support of a discovery Indoleamine 2,3 dioxygenase program.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1207: 123305, 2022 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-35839627
ABSTRACT
BMS-986205 (Linrodostat) is a small molecule inhibitor of Indoleamine 2, 3 dioxygenase (IDO) that is currently being evaluated in clinical trials for the oral treatment of advanced cancer. Initially, there were concerns regarding possible toxicity following administration, since BMS-986205 undergoes metabolism to form 4-chloroaniline. However, it was later determined that the downstream metabolites of 4-chloroaniline might be a greater concern. To evaluate the potential toxicity of these metabolites, a sensitive LC-MS/MS analytical method was needed to quantify both the parent compound and multiple metabolites. This presented a challenge since the method required the analysis of multiple analytes while still retaining the analytical sensitivity required to support studies. By utilizing a multi-function analytical method, we were able to quantify the necessary analytes using a complex LC-MS/MS-based method including the application of both negative and positive electrospray ionization.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Indoleamine-Pyrrole 2,3,-Dioxygenase
/
Tandem Mass Spectrometry
Language:
En
Journal:
J Chromatogr B Analyt Technol Biomed Life Sci
Journal subject:
ENGENHARIA BIOMEDICA
Year:
2022
Document type:
Article