RESUMO
AIM: Hemay005 is a novel small-molecule inhibitor of phosphodiesterase-4 developed for the treatment of psoriasis. Measurement of Hemay005 in biological samples is critical for evaluation of its pharmacokinetics in clinical studies. Methodology & results: Plasma and urine samples were extracted and then chromatographed on an Acquity UPLC HSS T3 column with a gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer using negative ESI. CONCLUSION: For the first time, a sensitive and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the quantitative determination of Hemay005 in human plasma and urine, and it was successfully applied to evaluate the pharmacokinetics of Hemay005 in healthy subjects in a first-in-human study.
Assuntos
Acetamidas/sangue , Acetamidas/urina , Análise Química do Sangue/métodos , Cromatografia Líquida de Alta Pressão/métodos , Pirróis/sangue , Pirróis/urina , Espectrometria de Massas em Tandem/métodos , Tiofenos/sangue , Tiofenos/urina , Urinálise/métodos , Acetamidas/farmacocinética , Métodos Analíticos de Preparação de Amostras , Humanos , Inibidores da Fosfodiesterase 4/sangue , Inibidores da Fosfodiesterase 4/farmacocinética , Inibidores da Fosfodiesterase 4/urina , Pirróis/farmacocinética , Reprodutibilidade dos Testes , Tiofenos/farmacocinéticaRESUMO
Stable and orally bio-available pro-drugs of CPS11 were synthesized. They are active on human umbilical vein endothelial cell proliferation assay and tube formation assay. The therapeutic efficacy and safety of 4 as a single agent or combined with Taxol in the treatment of MX-1 human breast cancer xenograft were evaluated. Compound 4 as a single agent failed to produce an anti-tumor activity, while it significantly enhanced antitumor potency of Taxol.
