Stereochemical determination of selegiline metabolites in postmortem biological specimens

In this study, findings related to an aircraft accident are reported. Biolo gical specimens collected at autopsy from the pilot of the fatal accident a nd two types of tablets found at the accident scene were submitted for toxi cological evaluation. It was determined that the pilot was dead at the cras h site and the cause of death was multiple traumatic injuries. The tablets were identified as selegiline and levodopa, commonly prescribed for the tre atment of Parkinson's disease. Selegiline, a stereospecific compound, is bi otransformed into(-)-N-desmethylselegiline, (-)-methamphetamine, and(-)-amp hetamine. The latter two levorotatory metabolites cannot be easily distingu ished by routine analysis from their dextrorotatory isomers, which are cont rolled substances. It was, therefore, prudent to differentiate these isomer s to determine if they resulted from the ingestion of a controlled substanc e, (+)-methamphetamine. Initial immunoassay drug screenings revealed the pr esence of amphetamine class drugs (867 ng/mL) in urine, amphetamine/methamp hetamine (261 ng/mL) in urine, and methamphetamine (46 ng/mL) in blood. The gas chromatography-mass spectrometry (GC/MS) results revealed the presence of methamphetamine in the concentrations of 76 ng/mL of blood and 685 ng/m L of urine. The concentration of amphetamine was 52 ng/mL in blood and 320 ng/mL in urine. To determine the stereospecificity of these amines, the iso lated amines from the biosamples were derivatized by a stereospecific agent , (S)-(-)-N- (trifluoroacetyl)-prolyl chloride, and characterized by a GC/M S method to be levorotatory. The 2.14 ratio of (-)-methamphetamine to (-)-a mphetamine concentrations in the urine was consistent with a selegiline stu dy in the recent literature. The stereospecific analysis, in conjunction wi th the history of the pilot bei ng on Parkinson's medications, suggests tha t the source of these amines was selegiline. This conclusion substantiates the importance of the identification of enantiomers in evaluating and inter preting related analytical results for accident investigations.