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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 26, Number 3, April,
pp. 303-307
TECHNICAL NOTE: LC–MS–MS Analysis of the Neuroleptics
Clozapine, Flupentixol, Haloperidol, Penfluridol, Thioridazine, and Zuclopenthixol
in Hair Obtained from
Psychiatric Patients
Wolfgang Weinmann[1], Claudia Müller[1], Susanne
Vogt[1], and Andreas Frei[2]
[1]Institute of Legal Medicine, Klinikum der Albert-Ludwigs-Universität
Freiburg, Albertstr. 9, D-79104 Freiburg, Germany
[2] Centre of Psychiatry, Kantonspital Luzern, CH-6001 Luzern, Switzerland
Hair samples of psychiatric
patients were analyzed by liquid chromatography–tandem mass spectrometry
(LC–MS–MS) for the neuroleptics clozapine, flupentixol, haloperidol,
penfluridol, thioridazine, and zuclopenthixol. In the study, these neuroleptics
were administered to the patients regularly for a minimum of six months. Sample
preparation was performed by washing, powdering with a ball mill, extraction
of drugs from hair by ultrasonication with methanol, cleanup by solid-phase
extraction and subsequent LC–MS–MS analysis using multiple reaction
monitoring (MRM). Calibration was performed for all drugs in the range of 0.05
to 10 ng/mg using spiked hair powder and doxepin-d3 as internal standard. Twenty
to 50 mg of hair powder was used and the detection limits of LC–MS–MS
were below 0.05 ng/mg for all drugs tested. Therapeutic dosage, number of subjects,
hair color, and detected amounts of drugs were as follows: clozapine (150–400
mg/day; n = 3, light brown, medium brown, black; 0.47–0.92 ng/mg), haloperidol
(150 mg/3 weeks; n = 1, black/gray; 12.2 ng/mg), penfluridol (20–30 mg/week;
n = 2, medium brown, black; 0.08 ng/mg; not detected in one case), thioridazine
(100–400 mg/day; n = 4, light brown, medium brown, black; 0.33–9.91
ng/mg, not detected in one case). Besides the active drugs also the desmethyl-metabolites
of clozapine and thioridazine were detected by LC–MS–MS. However,
flupentixol (5 mg/day; light brown hair) and zuclopenthixol (350 mg/3 weeks;
light brown hair) were not detected by these methods in one case each, although
the drugs were administered regularly to these patients. The comparison of dosage
and hair color in two cases with thioridazine and penfluridol suggests that
other interindividual factors may have an influence on drug concentration in
hair. Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
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