Distribution of topiramate in a medical examiner's case

Abstract

Topimarate (Topamax®) is a novel antiepileptic drug. Its mode of action is multifactorial and involves blockage of voltage-dependent sodium channels. The drug was detected in a 15-year-old epileptic who died soon after switching seizure prescriptions. Topimarate was recovered by basic extraction with ethyl acetate and analyzed by gas chromatography-mass spectrometry using selected ion monitoring: Ions monitored were m/z 324 and m/z 110 for topiramate and m/z 98 for the internal standard mepivacane. The drug was quantitated in blood, vitreous humor, bile, stomach content, and liver: the concentrations were 8.9, 12.4, and 10.9 mg/L, 31 mg/total content, and 29 mg/kg, respectively. Topiramate was detected in urine but not quantitated. Other drugs identified in this case were 0.45 mg/L nordiazepam and 0.05 mg/L oxazepam in blood. No alcohol was detected in any of the specimens. The cause of death was seizure disorder with upper respiratory infection. The manner of death was determined as natural. To our knowledge, this is the first report of the presence of topiramate in postmortem specimens.