Bioanalysis of INCB000928 in human saliva: nonspecific binding and inhomogeneous concentration.
Bioanalysis
; 14(7): 405-419, 2022 Apr.
Article
in En
| MEDLINE
| ID: mdl-35264018
ABSTRACT
Aim:
To develop a bioanalytical method for quantifying INCB000928 in human saliva. Materials &methods:
Human centrifuged saliva and human whole saliva were compared for matrix selection. Protein precipitation extraction and HPLC-MS/MS was used for analysis. Results &conclusion:
Nonspecific binding of INCB000928 was reduced in whole versus centrifuged saliva. Whole saliva was a preferred matrix for INCB000928 bioanalytical method validation. Incurred sample reanalysis (ISR) using a successfully validated method failed in a healthy volunteer study because of inhomogeneous INCB000928 concentration across sample tube depths. Individual mixing of sample tubes followed by immediate aliquoting corrected the ISR failure, with 97.2% of repeats passing versus 41.7% for the same ISR samples.
Fibrodysplasia ossificans progressiva (FOP) is a very rare condition where bone forms outside the skeleton (ossification), leading to restricted movement, decreased quality of life and shortened life span. Mutations in a gene called ALK2 have been identified as causing FOP. INCB000928 is a novel drug (to be taken by mouth) which inhibits ALK2 activity and prevents ossification in a laboratory mouse model of FOP. Because monitoring of the levels and efficacy of a drug often requires blood draws, which can be taxing in patients with FOP, this study aimed to develop a method to measure INCB000928 levels in saliva. The authors propose a unique procedure to process saliva samples to ensure accurate, reproducible quantitation of INCB000928 levels in saliva.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Saliva
/
Myositis Ossificans
Limits:
Humans
Language:
En
Year:
2022
Type:
Article