Factors affecting the stability of drugs and drug metabolites in biological matrices

Abstract

Evaluation of the stability of drugs and drug metabolites in a biological matrix is a critical element to bioanalytical method validation. It is critical to understand the most common factors that affect the stability of such analytes in order to properly develop methods for their detection and measurement. The degradation of drugs and drug metabolites in samples can occur through either reversible or irreversible processes. Common factors that affect this stability include temperature, light, pH, oxidation and enzymatic degradation. Special considerations are also required when dealing with chiral molecules, deuterated internal standards and large biomolecules. Relevant examples of these degradation effects and approaches for dealing with them are presented is this review as taken from the fields of pharmaceutical testing, clinical research and forensic analysis. It is demonstrated through these examples how an understanding of the chemical and physical factors that affect sample stability can be used to avoid stability problems and to create robust and accurate methods for the analysis of drugs and related compounds.