Cerebrospinal fluid as a post-mortem toxicological matrix: qualitative reliability and quantitative limitations in a cocaine-positive cases

Background in forensic toxicology, the detection of pharmacologically active exogenous substances is routinely performed. Interpretation of analyte concentrations must consider multiple variables, markedly affected by diffusion and degradation. These factors complicate toxicological assessment and have stimulated interest in alternative substrates. OBJECTIVE: To assess the toxicological informativeness of cerebrospinal fluid (CSF) through comparison with standard post-mortem matrices, and to investigate whether quantitative relationships exist between CSF and femoral blood concentrations of cocaine and benzoylecgonine. METHODS: CSF and standard toxicological matrices were collected from 10 forensic cases and three controls. All specimens underwent solid-phase extraction followed by HPLC-Orbitrap mass spectrometry for detection and quantification of cocaine, benzoylecgonine, and other relevant substances. RESULTS: Cocaine and benzoylecgonine were consistently detected in cerebrospinal fluid whenever present in standard matrices, indicating their passage across the blood-brain barrier and supporting CSF as a reliable alternative post-mortem matrix. However, the limited sample size and absence of temporal or clinical information precluded robust quantitative interpretation, highlighting the need for larger studies to clarify pharmacokinetic relationships. CONCLUSION: Cocaine and benzoylecgonine are detectable in cerebrospinal fluid when present in peripheral blood, but no stable proportional relationship allowing quantitative extrapolation from CSF to femoral blood could be established.