Nanostructure initiator mass spectrometry: tissue imaging and direct biofluid analysis.

Nanostructure initiator mass spectrometry (NIMS) is a recently introduced matrix-free desorption/ionization platform that requires minimal sample preparation. Its application to xenobiotics and endogenous metabolites in tissues is demonstrated, where clozapine and N-desmethylclozapine were observed from mouse and rat brain sections. It has also been applied to direct biofluid analysis where ketamine and norketamine were observed from plasma and urine. Detection of xenobiotics from biofluids was made even more effective using a novel NIMS on-surface extraction method taking advantage of the hydrophobic nature of the initiator. Linear response and limit of detection were also evaluated for xenobiotics such as methamphetamine, codeine, alprazolam, and morphine, revealing that NIMS can be used for quantitative analysis. Overall, our results demonstrate the capacity of NIMS to perform sensitive, simple, and rapid analyses from highly complex biological tissues and fluids.

Comparative assessment of blood and urine analyses in patients with acute poisonings by medical, narcotic substances and alcohol in clinical toxicology.

Acute poisonings by medical, narcotic substances and alcohol are actual in Russia in the recent years. Comparison of analytic facilities of modern analytical techniques: chromatographic (HPLC, GC, GC-MS) and immuno-chemical (FPIA) in clinical toxicology for urgent diagnostics, assessment of the severity of acute poisoning and the efficacy of the treatment in patients with acute poisonings by psychotropic drugs, narcotics and alcohol have been done. The object of the study were serum, blood, urine of 611 patients with acute poisonings by amitriptyline, clozapine, carbamazepine, opiates and also alcohol. Threshold concentrations (threshold, critical and lethal) of the toxicants and their active metabolites which corresponded to different degrees of poisoning severity have been determined. The most comfortable and informative screening method for express diagnostics and assessment of severity of acute poisonings by psychotropic drugs and narcotics showed the HPLC with using automatic analyzers. FPIA using the automatic analyzer could be applied for screening studies, if group identification is enough. GC-FID method is advisable in case of poisoning by medical substances and narcotics in view of repeated investigation for assessment of the efficacy of the therapy. GC-MS could be advisable for confirming the results of other methods. GC-TCD possess high sensitivity and specificity and is optimal for express differential diagnostics and quantitative assessment of acute poisoning by ethanol and other alcohols.

Thermal degradation of clozapine-N-oxide to clozapine during gas chromatographic analysis.

Studies were undertaken to determine if clozapine-N-oxide, the principal urinary metabolite of the antipsychotic agent clozapine, may interfere with the gas chromatographic-mass spectrometric bioanalysis of clozapine. Following injection of clozapine-N-oxide onto a (5% phenyl)methylpolysiloxane capillary column operated at 250 degrees C, significant on-column reduction of clozapine-N-oxide to the parent drug occurred. Accordingly, preparation of biological samples for clozapine determination by gas chromatography should avoid conditions which reportedly co-extract the N-oxide to assure no artifactual contribution of this metabolite in the detection of clozapine.