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1.
Bioanalysis ; 16(6): 347-362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38376139

RESUMO

Background: It has become common practice to assess solute carrier transporter (SLC)-mediated drug-drug interactions (DDIs) by quantitating various individual endogenous compounds as biomarkers in human plasma and urine. The goal of this work was to develop biomarker multiplex assays that could be utilized during first in human studies to support the simultaneous assessment of clinical DDI risk across various SLCs. Methodology: Hydrophilic interaction chromatography-MS/MS methods were developed, and validations were performed. Results: The multiplex assays were applied to a first in human study. Placebo/reference subject biomarker data were consistent with single assay in-house and published data. Conclusion: This work demonstrates the utility of these multiplex methods to support the concurrent evaluation of clinical DDI risk across various SLCs.


Assuntos
Espectrometria de Massa com Cromatografia Líquida , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Biomarcadores , Proteínas de Membrana Transportadoras , Interações Medicamentosas
2.
Bioanalysis ; 16(11): 545-555, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-39088035

RESUMO

Aim: The purpose of this work was to determine the feasibility of supporting a clinical microdose study for PF-06882961 (danuglipron), an oral small molecule agonist of the GLP-1 receptor, by LC-MS/MS. Methodology: Statistical instrument parameter optimization using response surface methodology was employed to develop a LC-MS/MS method for the analyte, PF-06882961. Results: An LC-MS/MS method was developed and validated to support a proof of concept microdose pharmacokinetics preclinical study in monkeys, administered PF-06882961 (0.005 mg total, average dose = 0.0007 mg/kg) via intravenous bolus injection. Conclusion: The present study demonstrated the feasibility of analyzing human microdose plasma samples for PF-06882961 by LC-MS/MS, instead of accelerator mass spectrometry, thereby reducing cost and eliminating synthesis and exposure to 14C labeled material.


[Box: see text].


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1 , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Cromatografia Líquida/métodos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Espectrometria de Massa com Cromatografia Líquida
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