Postmortem distribution of the novel antipsychotic drug quetiapine.
The objective of this research was to determine the concentrations and distribution of the atypical antipsychotic drug, quetiapine, in postmortem tissues from eight Medical Examiner cases. Quetiapine was isolated from liquid specimens and tissue homogenates by extraction at an alkaline pH into 1-chlorobutane. The 1-chlorobutane was decanted, and quetiapine, plus the internal standard (prochlorperazine), was back-extracted into 0.1N sulfuric acid. The acid layer was made basic, and quetiapine, plus the internal standard, was re-extracted into 1-chlorobutane. Quantitation was by gradient, high-pressure liquid chromatography on a C-8 ODS (2.1 x 150 mm, 5 mu) column with acetonitrile/0.1M ammonium hydroxide (pH 10) mobile phase and a photodiode array detector set at 258 nm. The apparent linear range of the assay was from 0.05 to 5.0 microg/mL. At known concentrations of 0.1 and 0.5, interday accuracy (n = 5) was 103.8 and 107.2%, respectively. Interday precision (% cv) at the same concentrations was 9.8 and 9.0, respectively. In the cases where quetiapine was not considered to have contributed to the death, the postmortem concentrations in blood, liver, and bile ranged between 0.15 and 2.7 mg/L (n = 6), 1.3 and 9.5 mg/kg (n = 8), and 10 and 46 mg/L (n = 5), respectively. In the one case involving a quetiapine overdose, concentrations in blood (19.8 mg/L), liver (12.6 mg/kg), and bile (161 mg/L) exceeded the ranges of concentrations determined in specimens from the quetiapine-unrelated deaths.
Hopenwasser
Jay
J
College of Criminal Justice, Sam Houston State University, Huntsville, TX 77341, USA.
Mozayani
Ashraf
A
Danielson
Terry J
TJ
Harbin
Jeremy
J
Narula
Harminder S
HS
Posey
Douglas H
DH
Shrode
Paul W
PW
Wilson
Stephen K
SK
Li
Richard
R
Sanchez
Luis A
LA
D014150:Antipsychotic Agents / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D001344:Autopsy; D001646:Bile / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003987:Dibenzothiazepines / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D005260:Female; D005554:Forensic Medicine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008297:Male; D000069348:Quetiapine Fumarate; D012015:Reference Standards; D014018:Tissue Distribution
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate