During nonclinical regulated toxicology studies, blood processing protocol deviations may negatively impact sample integrity and bioanalytical results. Standard practices for resolution of blood processing issues are not well established across the industry. In this article, using an illustrative example, we present a systematic approach to investigate and assess the impact of nonclinical blood processing protocol deviations that involve: assessment of the potential impact of deviations on toxicokinetic evaluation, performance of additional blood processing stability tests to ensure study sample integrity and establishment of study sample results reporting procedures to meet both scientific and regulatory quality requirements. This thorough and systematic approach can serve as a model for other analogous situations.