Doxepin and nordoxepin concentrations in body fluids and tissues in doxepin associated deaths.
Body fluids and tissues in eight doxepin (Dox)-related deaths were investigated in order to prove whether the individual concentration of Dox, the concentration sum of parent drug and its active metabolite N-desmethyldoxepin (NDox) or the concentration ratio Dox/Ndox valuably contribute to making a cause of death determination. Individual case histories were shortly described. Dox and NDox concentrations were determined by LC-MS/MS. Dox concentration measured from two cases was well within a concentration range considered therapeutic, whereas subtherapeutic dosing may have occurred in another two cases. There were two cases of fatal Dox ingestion, as well as a case of high dosage and advanced putrefaction, respectively. The liver concentration sum may be more useful if a fatal ingestion cannot be clearly separated from a person's medication usage. High concentrations could be observed in lung tissue, and combined concentrations of Dox and NDox may also be helpful in making a cause of death determination. There was a trend to a higher concentration sum in the brain with increasing combined levels in blood. Overall, the sum of the absolute figures allows a more accurate interpretation in Dox-related deaths as compared to the molar concentration ratio which may be helpful in acute ingestion. Determination of the N-desmethyl metabolite along with its parent is recommended and analysis should include more than a single specimen.
Gronewold
Antonia
A
Institute of Legal and Traffic Medicine, University Hospital, Voss-Str. 2, 69115 Heidelberg, Germany.
Dettling
Andrea
A
Haffner
Hans T
HT
Skopp
Gisela
G
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000032:analysis* / Q000506:poisoning*; D001646:Bile / Q000737:chemistry; D001923:Brain Chemistry; D002853:Chromatography, Liquid; D004316:Doxepin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000506:poisoning*; D005260:Female; D053593:Forensic Toxicology; D005766:Gastrointestinal Contents / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry; D019966:Substance-Related Disorders / Q000150:complications
D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin; C028701:desmethyldoxepin