Biotherapeutic drugs have emerged in quantity in pharmaceutical pipelines, and increasingly diverse biomolecules are progressed through preclinical and clinical development. As purification, separation, mass spectrometer detection and data processing capabilities improve, there is opportunity to monitor drug concentration by traditional ligand-binding assay or MS measurement and to monitor metabolism, catabolism or other biomolecular mass variants […]
Aim: To investigate the efficiency of two new fast-acting enzymes, recombinant arylsulfatase (IMCS-PSF) and mutant β-glucuronidase from Escherichia coli (IMCSzyme), in hydrolyzing specific terbutaline metabolites. Materials & methods: Two purified novel enzymes are used to precisely determine the amount of each metabolite in urine at different time points after oral administration. After systematically evaluating the
Background: Hybrid ligand-binding (LB) LC–MS/MS protein quantitative assays involve a LB step for analyte enrichment that has less stringent requirements than the conventional LB assays. Results: Herceptin™(trastuzumab) binding to HER2 extracellular domain was evaluated using on-bead and off-bead capture formats. The two formats yielded significantly different trastuzumab concentrations in human and monkey serum pharmacokinetic samples.
Aim: A sensitive method to quantify emixustat and its rapidly formed three major deaminated metabolites in human plasma was necessary to determine exposure in clinical trials. Methods: An LC–MS/MS method was validated for accuracy and precision, linearity, carry over, selectivity, recovery, matrix effects, hematocrit effects and stability. Results: A quantitative procedure for the determination of
The 2018 12th Workshop on Recent Issues in Bioanalysis (12th WRIB) took place in Philadelphia, PA, USA on April 9–13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. As usual,
Incurred sample reanalysis (ISR) is used to ensure the validity and reliability of bioanalytical data. Additionally, ISR results also help identify issues that could influence or bias the data. Overall, based on a decade of experimental data generated at Eli Lilly and Company, ISR failures are few with less than 5% of ISR samples failing
Within our company, incurred sample reproducibility (ISR) was implemented a decade ago. Only 11 studies (<2%) with failed ISR were identified over that period. These cases are described along with the strategy followed to resolve the issue. For three studies the failing ISR was caused by a method failure and all instances could be traced
In this paper, experiences and learnings are shared from the 10-year application of incurred sample reanalysis (ISR) in support of the AstraZeneca small molecule portfolio. The conclusions from including ISR in every clinical bioanalysis study for a period of 5 years, generating ISR data from 550 studies, are shared. Our preclinical ISR approach is described
With 10 years of experiences on incurred sample reanalysis (ISR) as an integrated part of regulated bioanalysis, the European Bioanalysis Forum has reflected on the implementation and the use of ISR. Three surveys were conducted in 2016 and 2017 as a revisit of the ISR experiences within European pharmaceutical industry and contract research organizations: has
For more than a decade, incurred sample reproducibility (ISR) has been one the most debated discussions in regulated bioanalysis. By in large, the industry acknowledges the value and importance of ISR to ensure the reproducibility of a newly developed method as a postvalidation experiment when applied for the first-time incurred samples. However, concerns remain about