Identification of selected psychopharmaceuticals and their metabolites in hair by LC/ESI-CID/MS and LC/MS/MS.

Hair samples of patients of psychiatry and hair samples of suicide cases were analysed by liquid-chromatography/ionspray-mass spectrometry (LC/MS) for antidepressants and neuroleptics. Electrospray ionisation (ESI) with in-source collision induced dissociation (ESI/CID) and tandem-mass spectrometry (MS/MS) were used for drug and metabolite identification. Mass spectra library searching was performed using an ESI/CID mass spectra library and a MS/MS spectra library. Furthermore, extracted ion chromatograms were used for the detection of N-desmethyl-metabolites, which were also identified by their fragment-ion spectra. Three examples using these methods are shown: The tricyclic antidepressant maprotiline, the selective serotonin receptor inhibitor (SSRI) citalopram and their desmethylmetabolites as well as the neuroleptic pipamperone were detected and identified in hair extracts. For extraction powdered hair was treated by ultrasonication in methanol and solid-phase extraction was used for sample clean-up prior to LC/MS or MS/MS analysis. These examples demonstrate the power of LC/MS and LC/MS/MS for the detection and identification of drugs in hair extracts using full-scan mode and ESI/CID with library searching or using highly selective LC/MS/MS-analysis with library searching or in multiple reaction monitoring mode.

Gas chromatographic examination of postmortem specimens after maprotiline intoxication.

Ingestion of an unknown quantity of Ludiomil (maprotiline)-costed tablets in a suicide is described. Although maprotiline is known for over 20 years now, relatively few cases of intoxications due to maprotiline overdose have been reported. The authors report a new and quick method to analyze and determine maprotiline and N-desmethylmaprotiline concentration in body fluids and postmortem specimens. The analytes and an internal standard (amitriptyline) were extracted from alkalinized samples into ethyl acetate before GC-NPD analysis. The proposed method resulted in a rapid procedure most useful in cases of deliberate poisoning with the tetracyclic antidepressant drug Ludiomil.

Determination of the antidepressant levoprotiline and its N-desmethyl metabolite in biological fluids by gas chromatography/mass spectrometry.

A specific and sensitive gas chromatographic/mass spectrometric method was developed and validated for the determination of the antidepressant levoprotiline in blood, plasma and urine and the simultaneous determination of levoprotiline and its desmethyl metabolite in urine. Deuterium-labelled analogues were used as internal standards. The compounds were isolated from the biological fluids by liquid-liquid extraction under basic conditions. Following derivatization with perfluoropropionic anhydride, the samples were analysed by capillary column gas chromatography/electron impact mass spectrometry with selected ion monitoring. The analysis of spiked samples demonstrated the high accuracy and precision of the method. Blood concentrations of levoprotiline down to 0.7 nmol l-1 (1 ml used for analysis) could be quantified with a coefficient of variation of 10% or less. The method is suitable for use in pharmacokinetic and bioavailability studies of levoprotiline in humans.

Effective column extraction from decomposed tissue in a suspected overdose case involving maprotiline and amitriptyline.

This paper describes the use of a Celite 560 column extraction technique in the initial separation of drugs from the contents of the skull of a severely decomposed body. Analysis of the extract obtained resulted in the determination of the presence of amitriptyline, and maprotiline and two of its metabolites. As a consequence, the laboratory was able to provide the medical examiner with information concerning an extremely difficult case.

Determination of maprotiline and N-desmethylmaprotiline from biological fluids by HPLC.

A reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous quantitation of maprotiline and its desmethylated metabolite from biological fluids. In this method, the samples were washed with hexane at acidic pH and then extracted with the same solvent at alkaline pH in the presence of an amine carrier. The drugs were eluted from the C18 column with acetonitrile (30%) in phosphate buffer (pH 2.5) and detected by their UV-absorbances at 205 nm. Peak identification was based on retention times and desmethyldoxepine was used as an internal standard for quantitation. Possible interferences were few; sensitivity (detection limit, 11 nmoles/L) and reproducibility (CV 2-2.5%) were good. Only about 10 minutes of chromatographic time was needed for one sample. Application for screening toxic drugs is suggested and briefly discussed.

Maprotiline fatality: case report and analytical determinations.

A new tetracyclic antidepressant drug, maprotiline hydrochloride was found to be the agent of death in a 23-year-old subject following massive injestion (4.5-6.0 g). The case may be the first reported maprotiline death (sole cause) in the United States. Analytical parameters were studies and various chromatographic and spectrophotometric systems are reported. Quantitation was performed by gas-liquid chromatography using a nitrogen-phosphorous detector. Concentrations of the compound in biological fluids and tissues are also reported.

Quantitative assay of maprotiline in biological fluids by gas-liquid chromatography.

A specific and sensitive gas-liquid chromatographic method has been developed for the assay of maprotiline in biological fluids. Maprotiline is isolated from the biological sample by base-specific extraction followed by conversion into the heptafluorobutyramide. The derivative is determined quantitatively by gas-liquid chromatography with an electron capture detector, nortriptyline being used as the internal standard. Amounts below 10 ng per biological sample can be measured.

[Fatal self-poisoning with the tetracyclic antidepressive drug, ludiomil (author's transl)]. / Tödliche Vergiftung mit dem "tetrazyklischen" Antidepressivum Ludiomil

The clinical and analytical data are presented of a case of severe Ludiomil self-poisoning (assumed total ingested dose: 3000 mg). Ludiomil resembles the tricyclic antidepressive drugs in regard to its toxic effects. Two essential observations made in Ludiomil poisoning are: 1) the limited therapeutic possibilities due to delayed elimination and 2) the severe degree of respiratory distress.