Aim
Drug concentrations in peripheral blood are most often used in interpretation of toxicological results in postmortem cases. However, peripheral blood is not always available or suitable for analysis, especially in advanced stages of decomposition. Therefore, other matrices than peripheral blood need to be investigated in order to reveal the cause of death. However, there is no obvious second choice. In this study, we analyzed postmortem femoral blood, cardiac blood, brain tissue and muscle tissue in order to investigate if drug concentrations in these alternative matrices were comparable to femoral blood and thereby useful for toxicological interpretation.

Method
A total of 104 consecutive autopsies where toxicological investigation was included were performed in a four-month period. Femoral blood (n = 89), cardiac blood (n = 85), brain tissue (n = 91) and muscle tissue (n = 104) were analyzed in all cases when available. Quantification of 69 common drugs and metabolites of toxicological interest was performed with four different multi-analyte methods all employing automated sample preparation and UHPLC MS/MS in MRM mode.

Results
In 104 autopsy cases, we were able to detect a total of 53 drugs and metabolites. Alternative matrix to femoral blood concentration ratios were calculated for 47 analytes for cardiac blood, 49 analytes for brain tissue and 50 analytes for muscle tissue, respectively. However, about half of the analytes were only detected in < 5 cases. Median ratios of analytes detected in ≥ 5 cases were determined to 0.59–1.9 (median = 1.1) for cardiac blood to femoral blood, 0.57–2.5 (median = 1.5) for brain tissue to femoral blood and 0.67–7.0 (median = 1.4) for muscle tissue to femoral blood. The largest deviation in ratios was observed for THC in muscle tissue. Here muscle tissue to femoral blood ratios varied from 2.3 to 20 with a median of 7.0 (n = 10). It is, however, a well-known fact that quantitative analysis of THC in muscle tissue is challenging, which our data also support. We therefore recommend that THC in muscle tissue should be reported as “detected” instead of a concentration.

Conclusion
Analysis of postmortem cardiac blood, brain tissue and muscle tissue revealed that concentrations were not directly comparable to those of femoral blood. However, 85% of the median ratios of alternative matrix to femoral blood of analytes detected in ≥ 5 cases, where in the range 0.5–2.0, and were therefore not markedly different. This demonstrates that interpretation of postmortem concentration in other matrices than femoral blood can be challenging and must be performed with caution.