False Carbamazepine Positives Due to 10,11-Dihydro-10-Hydroxycarbamazepine Breakdown in the GC–MS Injector Port

Abstract : During the investigation of aviation accidents, postmortem specimens from accident victims are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. A case recently received by CAMI screened positive for the anticonvulsant medication carbamazepine (Tegretol ) by gas chromatography/mass spectrometry (GC/MS). The carbamazepine found during the routine screening procedure was subsequently confirmed using a carbamazepine-specific GC/MS procedure. Concurrently, it was discovered that the accident victim had been prescribed oxcarbazepine (Trileptal ). Oxcarbazepine is nearly structurally identical to carbamazepine and is metabolized by cytosolic enzymes in the liver to the active compound 10,11-dihydro-10-hydroxycarbamazepine. The carbamazepine initially found in this case was present due to the breakdown of the active oxcarbazepine metabolite in the GC/MS injector port. In the current study, this conversion is investigated, the percentage of carbamazepine formed at various injector port temperatures is determined, and these three compounds are quantified in nine fluid and tissue specimens from the case in question. Finally, liquid chromatography/mass spectrometry (LC/MS) was used to demonstrate the absence of carbamazepine, and its formation, in the same specimens.