Handling unstable analytes: literature review and expert panel survey by the Japan Bioanalysis Forum Discussion Group.

Analyzing unstable small molecule drugs and metabolites in blood continues to be challenging for bioanalysis. Although scientific countermeasures such as immediate cooling, immediate freezing, addition of enzyme inhibitors, pH adjustment, dried blood spot or derivatization have been developed, selecting the best practices has become an issue in the pharmaceutical industry as the number of drugs with such problems is increasing, even for generic drugs. In this study, we conducted a comprehensive literature review and a questionnaire survey to determine a suitable practice for evaluating instability and implementing countermeasures. Three areas of focus, matrix selection, effect of hemolysis and selection of esterase inhibitors, are discussed.

Proposed selection strategy of surrogate matrix to quantify endogenous substances by Japan Bioanalysis Forum DG2015-15.

It is important to select an appropriate surrogate matrix for preparing calibration standards and quality control samples while quantitatively assaying for endogenous substances, because a blank matrix that does not contain the endogenous substance cannot be derived from the species from which the target study samples are collected. This is because the assay results might be affected, depending on the characteristics of the analyte in the surrogate matrix. Our discussion group that participated in the Japan Bioanalysis Forum discussed the recommended selection strategies, focusing on large and small molecules in ligand binding assays and LC-MS, respectively. We established an efficient selection strategy for a surrogate matrix, with simple compositions as the first candidates stated in this article.