Postmortem distribution of a-pyrrolidinovalerophenone and its metabolite in body fluids and solid tissues in a fatal poisoning case measured by LC-MS-MS with the standard addition method

摘要

We experienced an autopsy case, in which the cause of death was judged as a-pyrrolidinovalerophenone (a-PVP) poisoning. Other drugs or poisons that could have caused the death were not detected by our screening using gas chromatography-mass spectrometry. The deceased was a 41-year-old man. The postmortem interval was about 40 h. Cardiac blood, femoral vein blood, urine, stomach contents, and seven solid tissues were collected and frozen until analysis to investigate the distribution of a-PVP and its metabolite l-phenyl-2-(pyrrolidin-l-yl)pentan-l-ol (OH-alpha-PVP) in the body of the cadaver. After sample pretreatment, they were subjected to solid-phase extraction with Oasis HLB cartridges and analysis by liquid chro-matography-tandem mass spectrometry. Because the distribution study dealt with different matrices, we used the standard addition method to overcome the matrix effects. The concentration of a-PVP in urine was much higher than in other specimens; the concentrations of a-PVP in solid tissues except for the spleen were about twofold those in blood specimens. Among the solid tissues, the highest a-PVP concentration was found in the pancreas, followed by the kidney. The extremely high concentration of the drug in urine and the relatively high concentration in the kidney suggested that a-PVP is rapidly excreted into urine via the kidney. The distribution profile of OH-a-PVP was generally similar to that of a-PVP in body fluids and solid tissues. The concentration of OH-a-PVP in urine was also much higher than those in other specimens. Among the solid tissues, the OH-a-PVP concentration was highest in the liver, followed by the kidney. The high concentration of OH-a-PVP in the liver was expected, because the metabolism of a-PVP was probably most active in the liver. The high levels of OH-a-PVP in urine and kidney also suggested that the metabolite was also rapidly excreted into urine via the kidney. To test whether conjugated metabolites were present in urine and solid tissues, urine and homogenates of the liver and spleen were incubated with (3-glucuronidase/sulfatase at 37 degC for 5 h. Concentrations of OH-a-PVP were measured before and after the incubation, but differences in the concentrations before and after the incubation were within 10 % for the urine, liver, and spleen samples. To date, data on the distribution of a-PVP and OH-a-PVP in body fluids and solid tissues in a fatal a-PVP poisoning case have not been reported; thus, the findings of our study will be useful for assessment of future cases of a-PVP poisoning.