The Impact of Hemolysis on Stability of N -Desethyloxybutynin in Human Plasma

Abstract

Aim: Stability must be evaluated before quantitation of drugs or metabolites concentrations in biological matrices. We reported a case study where instability of a drug metabolite was mediated by hemolysis. Materials & methods: The instability of both enantiomers of N-desethyloxybutynin was observed in hemolyzed plasma stored at -20°C. The investigations indicated that heme-mediated oxidation converted the metabolite to its N-oxide. Storing samples under lower temperature (-50°C or below) or treatment with the antioxidant ascorbic acid stabilized the metabolite. Conclusion: The evaluation of the stability of some analytes in a hemolyzed sample is crucial as it may negatively impact incurred sample reanalysis or pharmacokinetic profiles on highly hemolyzed samples.

Perspectives on updates, clarifications and controversies in chromatographic assay guidance for bioanalytical method validation from major regulatory agencies and organizations

“…As such, there is also an argument to be made for inclusion of hemolyzed (and potentially lipemic) samples in regular stability assessments, owing to their potential to act as catalysts in analyte degradation. (Miao, Tan, Wells, & Unger, 2019). Still, WBS should be tested over the duration of time that the collected samples are in queue for processing.…”