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 (CBZ; Tegretol®) by gas chromatography-mass spectrometry (GC-MS). The CBZ found during this routine screening procedure was subsequently confirmed using a CBZ-specific GC-MS procedure. It was later discovered that the accident victim had been prescribed oxcarbazepine (OXCBZ; Trileptal®). OXCBZ is structurally similar to CBZ and is metabolized by cytosolic enzymes in the liver to an active metabolite, 10,11-dihydro-10-hydroxycarbamazepine (DiCBZ). It was determined that the CBZ initially found in this case was present due to the thermal breakdown of DiCBZ in the GC-MS injector port. In the current study, this conversion was investigated and the percentage of CBZ formed at various injector port temperatures was determined. Additionally, these three compounds were quantified in nine fluid and tissue specimens from the case in question. Liquid chromatography-mass spectrometry was also incorporated to further demonstrate the absence/presence of CBZ in these samples.