UHPLC-MS/MS bioanalysis of human plasma coproporphyrins as potential biomarkers for organic anion-transporting polypeptide-mediated drug interactions.
Bioanalysis
; 10(9): 633-644, 2018 May 01.
Article
em En
| MEDLINE
| ID: mdl-29749254
ABSTRACT
AIM:
Coproporphyrins (CP-I and CP-III) have been identified as possible biomarkers to predict human hepatic organic anion-transporting polypeptides-mediated-drug-interactions for a new drug entering clinical development.RESULTS:
The method is applicable to quantify plasma CP-I and CP-III within 0.078-15.0 nM. The results identify and address a number of challenges encountered with porphyrin assays such as photodegradation and interferences. To overcome interferences from ubiquitous porphyrins, a surrogate matrix was used to prepare calibration standards. Quality controls were prepared in plasma and surrogate matrix to ensure parallelism between surrogate matrix and plasma.CONCLUSION:
A robust UHPLC-MS/MS assay was developed and validated for CP-I and CP-III in plasma, and is currently applied to clinical studies to confirm suitability of Coproporphyrins as a potential substitute for drug-drug interaction study.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
/
Coproporfirinas
/
Transportadores de Ânions Orgânicos
/
Espectrometria de Massas em Tandem
/
Biomarcadores Farmacológicos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioanalysis
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos