Pipamperone concentrations and organ distribution in postmortem cases with and without overdoses

Pipamperone is a widely used antipsychotic, which can also be important in death cases. The interpretation of intoxication cases involving pipamperone remains difficult, due to limited postmortem and pharmacokinetic data. Hence, autopsy cases with pipamperone detection were examined regarding the organ distribution and postmortem redistribution (PMR). A liquid-liquid-chromatography with tandem mass spectrometry (LC-MS/MS) method for the detection of pipamperone in postmortem blood was developed and validated. Heart and femoral blood concentrations were determined in 32 autopsy cases, whereby organ distribution was determined in 12 cases. The method was applied to organ homogenates (brain, liver and kidney tissue), other body fluids (urine, cerebral spinal fluid (CSF)) and gastric content. Pipamperone concentrations of 0.82-19 mg/L were detected in femoral blood, 1.0-36 mg/L in heart blood. Heart and femoral blood ratios (H/F ratio) ranged from 0.5 to 3.9 (mean: 1.5 ± 0.8). Among organs, highest concentrations were determined in liver tissue (5.8-315 mg/kg). Concentrations in brain, CSF and urine/kidney were comparatively lower. The H/F ratios as well as the concentration differences in the organs and alternative body fluids lead to the assumption that pipamperone exhibits an insignificant to moderate PMR. A fatal intoxication, primarily caused by pipamperone was assumed in four cases, where the highest concentrations of pipamperone in blood (heart: 13.4-36 mg/L, femoral: 9.4-19 mg/L) were detected. Assuming a possible PMR for pipamperone, the interpretation of autopsy cases remains difficult. Drug concentrations must be assessed with care and an increase of postmortem concentrations must be considered.