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Bioanalysis ; 10(9): 633-644, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29749254

RESUMO

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.


Assuntos
Biomarcadores Farmacológicos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Coproporfirinas/sangue , Transportadores de Ânions Orgânicos/metabolismo , Espectrometria de Massas em Tandem/métodos , Biomarcadores Farmacológicos/química , Coproporfirinas/química , Desenho de Drogas , Interações de Medicamentos , Humanos , Transportadores de Ânions Orgânicos/química , Rifampina/sangue , Rifampina/química , Rosuvastatina Cálcica/sangue , Rosuvastatina Cálcica/química
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