Journal Article

More Reliable Brain Death Diagnosis With Chromatographic Analysis of Midazolam, Diazepam, Thiopentone, and Active Metabolites

Andreas Meinitzer, Winfried März, Harald Mangge and Gabriele Halwachs-Baumann

in Journal of Analytical Toxicology

Volume 30, issue 3, pages 196-201
Published in print April 2006 | ISSN: 0146-4760
Published online April 2006 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/30.3.196
More Reliable Brain Death Diagnosis With Chromatographic Analysis of Midazolam, Diazepam, Thiopentone, and Active Metabolites

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Brain death diagnosis may be confounded by centrally acting drugs. The certainty of brain death diagnosis can be enhanced by demonstrating that the concentrations of such drugs are well below the therapeutic range. A combined high-performance liquid chromatography-based method was developed for the benzodiazepines midazolam, 1-hydroxymidazolam, 1-hydroxymidazolam glucuronide, diazepam, and nordiazepam and for the barbiturates thiopentone and pentobarbitone in serum or plasma of critically ill patients. The lower limits of detection of the assays for benzodiazepines and barbiturates were 2.5 ng/mL and 0.05 µg/mL. The lower limits of the working ranges of these assays were set at 25 ng/mL and 0.5 µg/mL, respectively, and are below the lowest pharmacologically active plasma concentrations of these drugs. Intra- and interday coefficients of variations were less than 2.5% and 11.0% throughout, as determined with six replicates (n = 6). These assays were accurate in that the relative difference between actually measured and expected concentration never exceeded 12%. Utilization of these assays will render the diagnosis of brain death more reliable.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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