Characterization of postmortem γ-hydroxybutyric acid (GHB) and a novel model to discern exogenous use

Interpretation of postmortem (PM) γ-hydroxybutyric acid (GHB) remains challenging due to endogenous production and PM increases in concentration associated with decomposition. Existing interpretation guidelines primarily rely on a single criterion, such as concentration thresholds or urine-to-blood ratios. In San Francisco, routine and unbiased implementation of GHB testing across all casework generated a large dataset including 1865 GHB detections in PM blood or urine, of which 552 were paired peripheral blood and urine samples. Cases were categorized as acute exogenous use, confirmed exogenous use, or no indication of use based on toxicological and investigative findings. Peripheral blood concentrations in cases with no indication of use did not vary significantly by age, gender, race, or manner of death but were significantly higher in decomposed cases. While existing guidelines effectively identify endogenous levels, the proposed hybrid model, combining peripheral blood concentration (B) with urine-to-blood ratio (U/B), enables further classification into no exogenous use, possible exogenous use (B > 5 mg/L and U/B > -0.05 × B + 4), and acute exogenous use (B > 50 mg/L and U/B > -0.05 × B + 10). The model was evaluated and compared to existing guidelines. Internal applicability was assessed using recent casework, and external applicability was evaluated using an independent dataset from Québec, Canada. The hybrid model demonstrated improved performance, achieving substantially higher positive predictive value when compared to existing guidelines, while maintaining equal or improved performance measures across other metrics. This approach provides a conservative, evidence-based framework for distinguishing acute exogenous GHB use in PM casework.