Absorption, metabolism, and excretion of oral ¹⁴C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men.

The absorption, metabolism, and excretion of ibrutinib were investigated in healthy men after administration of a single oral dose of 140 mg of ¹⁴C-labeled ibrutinib. The mean (S.D.

High volume injections of biological samples for sensitive metabolite profiling and quantitation.

An online preconcentration approach was developed allowing the injection of very high volumes of biological samples, thereby greatly increasing sensitivity while maintaining LC resolution. The approach was applied to the analysis of radioactive samples from both in vitro and in vivo metabolism studies where typically the concentration of radioactivity given is often limited, while sample volume is usually not. The described online preconcentration approach reduces sample preparation and, therefore, also the risk for degradation and recovery issues often seen with offline preconcentration methods.

Identifying metabolite ions of peptide drugs in the presence of an in vivo matrix background.

Background: Peptides represent a growing class of potential drugs. Information on metabolic clearance can be valuable for peptide drug development but different challenges are encountered with the identification of peptide metabolites in comparison to the process used for small-molecule therapeutics.

Results: Enfuvirtide was selected as a test compound and dosed intravenously at 2 mg/kg to rats.

Speciation analysis of bromine-containing drug metabolites in feces samples from a human in vivo study by means of HPLC/ICP-MS combined with on-line isotope dilution.

The aim of this work was speciation analysis of metabolites in feces samples collected within a clinical study during which a bromine-containing anti-tuberculosis drug (TMC207) was administered to patients with multi-drug resistant tuberculosis infection. Owing to slow elimination of the drug, no (14)C label was used within this study. Quantification of the bromine species was accomplished using high performance liquid chromatography coupled to inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) in combination with on-line isotope dilution (on-line ID), while structural elucidation of the species was performed using HPLC coupled to electrospray ionization-mass spectrometry.

In vitro studies on the metabolism of trabectedin (YONDELIS) in monkey and man, including human CYP reaction phenotyping.

Trabectedin (YONDELIS) is a potent anticancer agent which was recently approved in Europe for the treatment of soft tissue sarcoma. The drug is currently also in clinical development for the treatment of ovarian carcinoma. In vitro experiments were conducted to investigate the hepatic metabolism of [(14)C]trabectedin in Cynomolgus monkey and human liver subcellular fractions.