Determination of Bromazepam in Blood by Electron-Capture GLC and of its Major Urinary Metabolites by Differential Pulse Polarography

Silva, J.Arthur F. De; Bekersky, Ihor; Brooks, Marvin A.; Weinfeld, Robert E.; Glover, William; Puglisi, Carl V.

doi:10.1002/jps.2600630923

Cited by 37 publications

(2 citation statements)

References 16 publications

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“…At the conclusion of the study, the blood samples were subjected to gas chromatographic analysis for diazepam and desmethyldiazepam 3 or for bromazepam. 4 The two assay methods differ in their limit of sensitivity, 1 ng/ml for diazepam and its metabolite and 10 ng/ml for bromazepam.…”

Section: Methodsmentioning

confidence: 99%

Blood levels and electroencephalographic effects of diazepam and bromazepam

Fink

Irwin

Weinfeld

et al. 1976

Clin Pharma and Therapeutics

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Blood levels and electroencephalographic (EEG) data were collected for 2 hr after single oral doses of bromazepam (9 mg), diazepam (10 mg), and placebo in 13 male adult volunteers. Both drugs caused an increase in beta activity (above 13 Hz) and a decrease in alpha activity (9 to 11 Hz) in the EEG. Blood levels of 100 ng/ml of diazepam or 50 ng/ml of bromazepam were associated with significant changes in EEG beta activity. Temporal changes in the EEG after administration of diazepam or bromazepam paralleled development of plasma levels of these drugs. Although a weakly significant correlation was found between measurable diazepam blood levels and amount of increased EEG beta activity, the relationship between measurable bromazepam blood levels and the degree of EEG changes was not significant. Quantitative EEG is a sensitive continuous response measure, useful in defining cerebral activity, response latency, and relative potency of psychoactive benzodiazepines.

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Section: Methodsmentioning

confidence: 99%

Blood levels and electroencephalographic effects of diazepam and bromazepam

Fink

Irwin

Weinfeld

et al. 1976

Clin Pharma and Therapeutics

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“…The commercial development of high temperature stable liquid phases [methyl phenyl silicone (OV-17), cyanosilicone (XE-60), fluorosilicone (QF-1), dimethylsilicone (OV-1), and the high temperature (400 °C) 63Ni-electron capture detector [operated in the pulsed (dc) mode with the capability of varying the dc voltage applied, the pulse rate and pulse width of the applied potential pulses] has made possible the highly sensitive and specific determination of these drugs as the intact moiety. Therefore, compounds, such as medazepam and diazepam (7), chlordiazepoxide (17), nitrazepam (18), bromazepam (19), clonazepam and flunitrazepam (20), flurazepam (21), and temazepam (22) are now analyzed as the intact 1,4-benzodiazepine or -diazepin-2-one with the desired sensitivity and specificity with simple derivatization reactions performed in those instances which requires it to improve volatility, peak shape, and EC-detector response (18,20,22).…”

Section: Resultsmentioning

confidence: 99%

Determination of 1,4-benzodiazepines and -diazepin-2-ones in blood by electron-capture gas-liquid chromatography

Ja¹,

Bekersky²,

Cv³

et al. 1976

Anal. Chem.

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137

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a Based on the concentration of material necessary to produce a signal twice the standard deviation of the random background noise. b Based on 10-µ1 sample.oxide-acetylene flame for any of the metals assayed, including chromium. The temperature change in the nitrous oxide-acetylene flame when aspirating different quantities of liquids apparently shows little or no effect on the free atom fraction in the flame.Detection Limits. In order for the AAS detector system to be useful in liquid chromatographic work, the detector must be both selective and sensitive. The selectivity and sensitivity of conventional AAS work has been well noted (10). This selectivity also applies to AAS when used as an LC detector and, while the range of compounds for which it is suitable is not as wide as other LC detectors, its specificity far surpasses that of other detectors. Difficulties can arise when using the detector for assays of several different metals, since lamp and burner changes are necessitated. Chromatograms of several species containing the same metal are, however, ideally suited for the detection system.The detection limits of this system were measured in the conventional manner, i.e., the concentration of material necessary to produce a signal twice as large as the standard deviation of the random background noise.The detection limits for several of the transition metals in both organic and aqueous phases are presented in Table IV. These values are applicable under the experimental conditions used and may be improved under more nearly optimum conditions. The conditions of the AAS, such as sensitivity and gain of the electronics, and adjustment of concentration control on the Perkin-Elmer AAS may allow lower detection limits for selected metals.Generally speaking, solutions containing metals in the mg/1. (part per million) range are satisfactory for this type of detection.The use of organic mobile phases requires some modification of the AAS for optimum performance. When aspirating organics, the three-slot burner head gave significantly better results than did the standard single-slot burner. A "hotter" (lower fuel-air ratio) flame could be generated with the three-slot burner, because of its ability to cope with a higher gas flow without excessive instability. The absolute detection limits in Table III are based on a 10-µ1 sample. Use of a larger sample loop would, of course, lower these figures.

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New synthesis of 7‐bromo‐1, 3‐dihydro‐3‐hydroxy‐5‐(2′‐pyridyl)‐2H‐1,4‐benzodiazepin‐2‐one

KOVAC¹,

BELIN²,

Fajdiga³

et al. 1981

Journal of Heterocyclic Chem

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A new synthesis of 7‐bromo‐1,3‐dihydro‐3‐hydroxy‐5‐(2′‐pyridyl)‐2H‐1,4‐benzodiazepin‐2‐one (5) is described. Starting from bromazepam (3), C(3) acylation with lead tetraacetate/potassium iodide in acetic acid affords 4, while its mild hydrolysis according to our recently described method (5) gives 5. Improved hexamine cyclization of 1 into 3, via quaternary hexaminium salt 2, is discussed, and identification of the intermediates 7 and 8 is performed. Compound 5 undergoes on melting, or on brief heating in glacial acetic acid, the thermal rearrangement into quinazolin‐2‐aldehyde (13), the structure of which is confirmed by oxidation into the ester 14, which in turn was hydrolyzed to the acid 15. The same compound (5) rearranges on heating with manganese(III) acetate in acetic acid into the 3‐amino‐2‐quinolone derivative 6. On heating in glacial acetic acid in the presence of lead tetraacetate/potassium iodide (or iodine), compound 4, in addition to giving the aldehyde 13, ester 14 and acid 15 rearrangement products, affords 1,2‐dihydroquinazolin‐2‐carboxylic acid 16.

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Determination of Bromazepam in Blood by Electron-Capture GLC and of its Major Urinary Metabolites by Differential Pulse Polarography

Cited by 37 publications

References 16 publications

Blood levels and electroencephalographic effects of diazepam and bromazepam

Blood levels and electroencephalographic effects of diazepam and bromazepam

Determination of 1,4-benzodiazepines and -diazepin-2-ones in blood by electron-capture gas-liquid chromatography

New synthesis of 7‐bromo‐1, 3‐dihydro‐3‐hydroxy‐5‐(2′‐pyridyl)‐2H‐1,4‐benzodiazepin‐2‐one

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