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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 32, Number 2, March,
pp.147-155
Quantitation
of Seven Low-Dosage Antipsychotic Drugs in Human Postmortem Blood
Using LC–MS–MS
M. Roman, R. Kronstrand, D. Lindstedt, and
M. Josefsson
Department of Forensic Genetics and Forensic Toxicology, National
Board of Forensic Medicine, Artillerigatan 12, SE-581 33 Linköping,
Sweden
In forensic toxicology, antipsychotic drugs are
of considerable interest because of their abuse potential and
their involvement in intoxications and suicides. In recent years,
several new drugs dosed at low levels have entered the market
and have put further demands on assays used. The aim of this
work was to develop a validated liquid chromatography–tandem
mass spectrometry assay for the quantitation of the low-dosage
antipsychotic drugs buspirone, fluphenazine, flupenthixol, perphenazine,
risperidone, ziprasidone, and zuclopenthixol in human postmortem
blood. After liquid–liquid extraction using methyl t-butyl
ether, compounds were separated on a Zorbax SB-CN column. Calibration
curves were linear in the range 0.8–100 µg/L (r > 0.998)
for all drugs. Both within- and between-day coefficients of variation
were lower than 25% for all drugs at the LOQ, and extraction
recoveries ranged between 58 and 112%. The possible presence
of matrix effects was closely investigated. Fifty-four authentic
samples were analyzed within the routine postmortem investigation,
which resulted in the diagnosis of three fatal intoxications.
Even though only a few intoxications were identified, the assay
may present valuable information on suicidal deaths in psychotic
patients where a true negative result implies noncompliance and
a higher susceptibility for suicide. Without a sensitive enough
method, this conclusion cannot be drawn. Therefore, we believe
that antipsychotic drugs must be measured not only in toxic concentrations
but also in therapeutic levels in postmortem cases.
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