Acidic hydrolysis of bromazepam studied by high performance liquid chromatography. Isolation and identification of its degradation products

Panderi, Irene; Archontaki, Helen; Gikas, Evagelos; Parissi-Poulou, M.

doi:10.1016/s0731-7085(97)00201-x

Cited by 21 publications

(16 citation statements)

References 21 publications

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“…The mechanism of acid hydrolysis of bromazepam proceeds through the intermediate N-(4-bromo-2(2-pyridylcarbonyl) phenyl)-2-aminoacetamide leading to the final products, 2-amino-5-bromobenzoyl pyridine and glycine. As it was reported, formation of the intermediate is very fast while the formation of the final product is rather slow [2].…”

Section: Hydrolysis Of Bromazepam Under Acidic Conditionmentioning

confidence: 52%

“…We followed Panderi et al [2] procedure to optimize the conditions for the chromatographic system and resulted in good separation efficiency such as good resolution between peaks, minimum tailing or fronting and retention time repeatability. …”

Section: Development and Optimization Of The Stability-indicating Hplmentioning

confidence: 99%

“…Bromazepam (C 14 H 10 BrN 3 O), chemically known as 7-bromo-1, 3-dihydro-5(2-pyridyl)-2H-1, 4-benzodiazepin-2-one, is a member of the 1, 4-benzodiazepine drug that was first synthesized by Fryer, in 1964 [2,3]. Bromazepam, like most of the benzodiazepine derivatives, is hydrolyzed in acidic aqueous solution leading to a series of degradation products [2].…”

Section: Introductionmentioning

confidence: 99%

“…Bromazepam, like most of the benzodiazepine derivatives, is hydrolyzed in acidic aqueous solution leading to a series of degradation products [2]. The rate of acidic hydrolysis of bromazepam is believed to be dependent on the state of protonation of the pyridyl and azomethine nitrogen atoms [4,5].…”

Section: Introductionmentioning

confidence: 99%

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High Performance Liquid Chromatography (HPLC) Stability Indicating Method for the Determination of Bromazepam Via its Copper (II) Chelates

Takele

Attaya²,

Hymete³

et al. 2017

PHARMSCI

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Introduction:Bromazepam is hydrolyzed in acidic aqueous solution leading to a series of degradation products. The rate of acidic hydrolysis is believed to be dependent on the state of protonation of the pyridyl and azomethine nitrogen atoms. Stability test is important in pharmaceutical industry to provide evidence on how the quality of an active substance or pharmaceutical product varies with time under the influence of a variety of environmental factors. Objective:The aim of the study was to develop a simple stability indicating method for the determination of bromazepam. Method:Bromazepam solution was prepared and forced degradation of bromazepam was performed under acid hydrolysis using sulphuric acid. High performance liquid chromatography determination of pure and degraded bromazepam and bromazepam-copper (II) complex was performed using reversed phase octyl C-8 column under isocratic conditions and the chromatographic conditions were set as follows; the flow rate of the mobile phase was 1.5 mL/min; injection volume was 10 μL, column temperature was 30 o C and the detector wavelength being 309 nm. Results:Bromazepam, its degradation product and bromazepam chelated with copper (II) were determined using the developed mobile phase with flow rate of 1.5 mL/min. Good separation with sharp peak, minimum tailing and retention time repeatability was obtained. The rate order, rate constant and half-life of degradation were also determined, and it was observed that the degradation reaction follows the first order kinetics. Conclusion:Chromatographic separation of bromazepam chelated with copper (II) was achieved and the method can be further used in drug manufacturing quality control.

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Section: Hydrolysis Of Bromazepam Under Acidic Conditionmentioning

confidence: 52%

Section: Development and Optimization Of The Stability-indicating Hplmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High Performance Liquid Chromatography (HPLC) Stability Indicating Method for the Determination of Bromazepam Via its Copper (II) Chelates

Takele

Attaya²,

Hymete³

et al. 2017

PHARMSCI

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“…Thus, the half-life of alprazolam in solution was notably higher than those of diazepam, oxazepam, nordiazepam, temazepam, and mainly midazolam and lorazepam, when they were irradiated with simulated sunlight, [16][17][18][19] which is coherent with the stability observed for alprazolam in the wileyonlinelibrary.com/journal/dta photodegradation assays carried out in this work. In the same way, although the different assays are not totally comparable, it can be stated that the acidic or alkaline hydrolysis of lorazepam, oxazepam, diazepam and bromazepam is easier than for alprazolam [12,[20][21][22][23][24][25] ; conversely, midazolam and clonazepam seem to be more resistant to hydrolysis than alprazolam. [20,26,27] Regarding the biological degradation, it has been reported that diazepam is not biotransformed by bacterio-plankton either in river water or in bacterial liquid cultures from amended soil [28,29] ; temazepam was also stable in the bacterial culture while ozaxepam underwent a partial biotransformation, about 40%.…”

Section: Resultsmentioning

confidence: 99%

Persistence of alprazolam in river water according to forced and non‐forced degradation assays: adsorption to sediment and long‐term degradation products

Jiménez

Sánchez

Muñoz

et al. 2017

Drug Testing and Analysis

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Alprazolam is a pharmaceutical compound that it is detected in surface waters. Some degradation studies in aqueous solutions and pharmaceutical products are available, but there is no reliable information about its stability in river water. Here, assays have been conducted under forced biological, photochemical, and thermal conditions, and under non-forced conditions, to estimate the fate of alprazolam in river water and know its degradation products. The forced assays indicated that the biological and photochemical degradation of alprazolam was negligible; heating at 70°C for a long time barely affected it. The degradation of alprazolam in river water at 100 μg/L was about 5% after 36 weeks, keeping the water under a natural day-night cycle at room temperature and limiting partially the exposure to sunlight as happens inside a body of water; no change in concentration was observed when the monitoring was performed at 2 μg/L. The results suggest the persistence of alprazolam in surface water and a possible accumulation over time. Residues were monitored by ultra-pressure liquid chromatography/quadrupole time-of-flight/mass spectrometry after solid-phase extraction; nine degradation products were found and the structures for most of them were proposed from the molecular formulae and fragmentation observed in high-resolution tandem mass spectra. (5-chloro-2-(3-methyl-4H-1,2,4-triazol-4-yl)phenyl)(phenyl)methanol was the main long-term transformation product in conditions that simulate those in a mass of water. The degradation rate in presence of sediment was equally very low under non-forced conditions; adsorption coefficients of alprazolam and major degradation products were calculated. Copyright © 2016 John Wiley & Sons, Ltd.

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Assays for Benzodiazepines

Bertol

Vaiano

2016

Neuropathology of Drug Addictions and Substance Misuse

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Acidic hydrolysis of bromazepam studied by high performance liquid chromatography. Isolation and identification of its degradation products

Cited by 21 publications

References 21 publications

High Performance Liquid Chromatography (HPLC) Stability Indicating Method for the Determination of Bromazepam Via its Copper (II) Chelates

High Performance Liquid Chromatography (HPLC) Stability Indicating Method for the Determination of Bromazepam Via its Copper (II) Chelates

Persistence of alprazolam in river water according to forced and non‐forced degradation assays: adsorption to sediment and long‐term degradation products

Assays for Benzodiazepines

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