Stereochemical determination of selegiline metabolites in postmortem biological specimens

In this study, findings related to an aircraft accident are reported. Biological specimens collected at autopsy from the pilot of the fatal accident and two types of tablets found at the accident scene were submitted for toxicological evaluation. It was determined that the pilot was dead at the crash site and the cause of death was multiple traumatic injuries. The tablets were identified as selegiline and levodopa, commonly prescribed for the treatment of Parkinson's disease. Selegiline, a stereospecific compound, is biotransformed into (-)-N-desmethylselegiline, (-)-methamphetamine, and (-)-amphetamine. The latter two levorotatory metabolites cannot be easily distinguished by routine analysis from their dextrorotatory isomers, which are controlled substances. It was, therefore, prudent to differentiate these isomers to determine if they resulted from the ingestion of a controlled substance, (+)-methamphetamine. Initial immunoassay drug screenings revealed the presence of amphetamine class drugs (867 ng/mL) in urine, amphetamine/methamphetamine (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/mL 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 isolated amines from the biosamples were derivatized by a stereospecific agent, (S)-(-)-N-(trifluoroacetyl)-prolyl chloride, and characterized by a GC/MS method to be levorotatory. The 2.14 ratio of (-)-methamphetamine to (-)-amphetamine concentrations in the urine was consistent with a selegiline study in the recent literature. The stereospecific analysis, in conjunction with the history of the pilot being on Parkinson's medications, suggests that the source of these amines was selegiline. This conclusion substantiates the importance of the identification of enantiomers in evaluating and interpreting related analytical results for accident investigations.