Determination of five quinolone antibiotic residues in foods by micellar electrokinetic capillary chromatography with quantum dot indirect laser-induced fluorescence.

A new assay was developed for the determination of five quinolone antibiotic residues in foods, loxacin, enrofloxacin, ciprofloxacin, lomefloxacin, and norfloxacin, by micellar electrokinetic capillary chromatography with indirect laser-induced fluorescence, in which cadmium telluride quantum dots were used as a fluorescent background substance. Some factors that affected the peak height and the resolution were examined. The optimized running buffer was composed of 20 mM SDS, 7.2 mg/L quantum dots, and 10 mM borate at pH 8.8. The separation voltage was 20 kV. Under these conditions, five quinolone antibiotic residues were separated successfully within 8 min. The detection limits ranged from 0.003 to 0.008 mg/kg; the linear dynamic ranges were all 0.01 ∼ 10 mg/kg; and the average recoveries of the spiked samples were 81.4 ∼ 94.6 %. The assay can meet the requirement of maximum residue limits to these five quinolone antibiotics in the regulations of the European Union and Japan and has been applied for determining their residues in animal-derived food.

Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in vitro binding and computational study.

The interaction of diazepine analogues like clozapine or olanzapine with D2 receptor was greatly affected by a mixture of HRP/H(2)O(2) known to induce the formation of nitrenium ion. Unlike diazepine derivatives, the oxidative mixture had low impact on the affinity of oxa- and thiazepine derivatives such as loxapine, clothiapine or JL13 for the D2 receptor. Molecular docking simulations revealed a huge difference between the mode of interaction of clozapine nitrenium ion and the parent drug. Electronic and geometric changes of the tricyclic ring system caused by the oxidation appeared to prevent the compound finding the correct binding mode and could therefore explain the difference observed in binding affinities.

Acute and chronic effects of neuroleptic drugs on plasma and brain homovanillic acid in the rat.

In the rat, the acute administration of the neuroleptic drug, haloperidol, produces a parallel increase in brain and plasma concentrations of the dopamine metabolite, homovanillic acid (HVA). The effect of other neuroleptic drugs, which may differ from haloperidol in their central and peripheral actions, on brain and plasma HVA has not been systematically investigated. Therefore, in this report we examine the acute effects of six different neuroleptic drugs, representing most major chemical classes of these drugs, on plasma and brain concentrations of HVA. Metoclopramide, fluphenazine, loxapine, and molindone produce parallel increases in brain and plasma HVA which closely resemble those produced by haloperidol. Compared to these neuroleptics, chlorpromazine produces a much greater increase in plasma HVA but a similar effect on brain HVA. The large chlorpromazine-induced increase in plasma HVA suggests that this drug alters peripheral production or clearance of HVA, perhaps via blockade of peripheral alpha-receptors. Of the available neuroleptics, sulpiride is one of the most specific and potent at blocking the dopamine vascular receptor. Administration of high doses of sulpiride produces only modest increases in both plasma and brain HVA, suggesting that blockade of peripheral dopamine receptors does not substantially alter peripheral clearance of HVA. After chronic administration of haloperidol for up to 21 days, plasma HVA continued to reflect the brain HVA response to drug administration.

GLC/MS assay for loxapine in human biofluids and tissues with deuterium labeled analog as an internal standard.

A quantitative gas liquid chromatographic-mass spectrometric (GLC/MS) assay was developed for the determination of loxapine in human blofluids and tissues. The assay utilizes selected ion monitoring in a GLC effluent of the molecular ion of loxapine generated by electron-impact ionization (EI). Loxapine-d3 was used as the internal standard. The assay can measure 2 ng/mL of loxapine with about 6% precision. The curve relating the amounts of loxapine added in control plasma versus the ion intensity ratio (m/e 327/330) over a large range of loxapine concentrations was linear with essentially zero intercept. The method was used for the analysis of loxapine in human urine, plasma, brain, liver, lung and spleen.

Acute loxapine intoxication in a child.

Thin-layer chromatography (TLC) was used to confirm the alleged ingestion of Loxitane (loxapine succinate) by a 20-month-old child. GC was used to further characterize TLC spots and to quantitate the loxapine concentration of the blood at 0.072 mg/dL, which was consistent with the child's presenting signs of lethargy and ataxia. The appropriate supportive symptomatic therapy, with monitoring for CNS and cardiovascular toxicities, resulted in an uneventful recovery.

Identification of misused drugs in the clinical laboratory. I. Tricyclics.

A systematic approach evaluating the abuse of tricyclic drugs in the hospital emergency room from the laboratory point of view is presented. This comprehensive screen involves qualitative colorimetric tests, ultraviolet (UV) spectrophotometry, thin layer chromatography (TLC), gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). Laboratories with varying facilities and resources can adapt the present screen. Amitriptyline, doxepin, loxapine and desipramine misuse were identified and confirmed using the proposed methodology in 14 cases. Increasing misuse of tricyclic antidepressants requires that the clinical laboratory have a systematic approach to identify and confirm the presence of these drugs in emergency room patients.