High-performance liquid chromatographic method with UV photodiode-array, fluorescence and mass spectrometric detection for simultaneous determination of galantamine and its phase I metabolites in biological samples

Maláková, Jana; Nobilis, Milan; Svoboda, Zbyněk; Lísa, Miroslav; Holčapek, Michal; Kvĕtina, J; Klimeš, Jiřı́; Palička, Vladimír

doi:10.1016/j.jchromb.2007.03.025

Cited by 37 publications

(32 citation statements)

References 22 publications

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“…Unfortunately, in the present study this solvent system did not allow the extraction of solute 5. Another study related to the phase I metabolism of 1 claimed the MS identification of 5 [18]. Although our MS data were in good agreement with earlier published data [18] (the recorded MS and MS n data can be found in Supplementary material S1), Table 2. the lack of additional NMR data, or other proof for the definitive identity of 5 required another strategy proving the N-oxides identity.…”

Section: Numbersupporting

confidence: 91%

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide

Marques

Maada

Kanter

et al. 2011

Journal of Pharmaceutical and Biomedical Analysis

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Section: Numbersupporting

confidence: 91%

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide

Marques

Maada

Kanter

et al. 2011

Journal of Pharmaceutical and Biomedical Analysis

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“…The product ion at m/z 348 was formed by the neutral loss of water (H 2 O, 18 Da), while the other fragment ion at m/z 309 was due to the neutral loss of methylvinylamine (C 3 H 7 N, 57 Da), which subsequently underwent another neutral of water (H 2 O, 18 Da) to produce fragment ion at m/z 291. The product ions as well as the fragmentation pathway apparently resembled the parent drug molecule galantamine hydrobromide [20] in most respects other than having an extra bromine atom. In addition to the brominated fragments, the MS 2 spectrum was also accompanied by daughter ions at m/z 256, m/z 230, and m/z 212 (Fig.…”

Section: Structural Elucidation Of Galantamine and Imp-a By Lc-ms/msmentioning

confidence: 92%

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSⁿand 2D-NMR

Thomas¹,

Paul²,

Agarwal³

et al. 2014

Acta Chromatographica

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Summary.Galantamine hydrobromide was subjected to oxidative stress degradation using hydrogen peroxide and analyzed as per the chromatographic conditions described in European Pharmacopoeia. The drug showed considerable degradation at ambient temperature resulting in the formation of two degradation products at relative retention times (RRTs) 0.63 and 2.52. The minor degradant at RRT 0.63 was identified as galantamine N-oxide. The principal degradant formed at RRT 2.52 was found to be unknown and has not been reported previously. The unknown impurity was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by isolation using semi-preparative high-performance liquid chromatography (HPLC). The isolated impurity was characterized using one-dimensional, two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D NMR) and elemental analysis (EA). The principal degradant was found to be formed due to the generation of bromine and subsequent attack on the aromatic ring via in situ reaction between hydrogen bromide and hydrogen peroxide. The unknown impurity was characterized as (4aS,6R,8aS)-5,6,9,10,11,12-hexahydro-1-bromo-3-methoxy-11-methyl-4aH-[1]benzofuro [3a,3,2-ef] [2] benzazepin-6-ol.

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“…In this research study, these compounds except Tacrine are picked up to understand the retention behaviour using variety of ion-pair reagents. There are many analytical methods for these compounds involving different techniques like RP-LC with UV [7,8], fluorescence detection and sodium octane sulphonate modifier [9,10], MS-MS [11][12][13] for the plasma and urine samples, chiral analysis for enantiomer separation [14] of these drug substances.…”

Section: Introductionmentioning

confidence: 99%

Rapid Screening of Volatile Ion-Pair Reagents Using UHPLC and Robust Analytical Method Development Using DoE for an Acetyl Cholinesterase Inhibitor: Galantamine HBr

et al. 2011

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As over 70% of pharmaceutical compounds are bases, the analysis of these basic compounds by high performance liquid chromatography (HPLC) continues to be of great value and interesting. Acetyl cholinesterase inhibitors (AChEIs), which contain the basic compounds like Rivastigmine tartrate, Galantamine hydrobromide and Donepezil with different polarities, were chosen for the study. A rapid screening of the volatile ion-pairing reagents was performed using modern techniques like ultra high performance liquid chromatography (UHPLC). The experiments were planned using the 'Design of Experiments' (DoE) approach to identify the LC-MS compatible ion-pair reagent. In this study, Heptafluorobutyric acid (HFBA) has given a very good peak shape with tailing factor at 1.4 and theoretical plates up to *5,000 were observed, compared to tailing factor at 1.9 and theoretical plates up to *3,000 with non-volatile ion-pair reagent sodium heptane sulphonate (SHS). Similarly retention with HFBA was optimum as *5 min in short run time method compared to *13 min with SHS. This ion-pair reagent has proved to be good replacement of sodium alkyl sulphonate modifiers. HFBA can also be used for semi-preparative work for isolation of impurities by just evaporating the solvents. It avoids the extraction of other inorganic modifiers.Keywords Ultra high performance liquid chromatography (UHPLC) Á Volatile ion-pair reagents Á Design of experiments (DoE) Á Acetylcholinesterase inhibitor (AChEI) Á Alzheimer's disease (AD)

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High-performance liquid chromatographic method with UV photodiode-array, fluorescence and mass spectrometric detection for simultaneous determination of galantamine and its phase I metabolites in biological samples

Cited by 37 publications

References 22 publications

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSⁿand 2D-NMR

Rapid Screening of Volatile Ion-Pair Reagents Using UHPLC and Robust Analytical Method Development Using DoE for an Acetyl Cholinesterase Inhibitor: Galantamine HBr

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High-performance liquid chromatographic method with UV photodiode-array, fluorescence and mass spectrometric detection for simultaneous determination of galantamine and its phase I metabolites in biological samples

Cited by 37 publications

References 22 publications

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSnand 2D-NMR

Rapid Screening of Volatile Ion-Pair Reagents Using UHPLC and Robust Analytical Method Development Using DoE for an Acetyl Cholinesterase Inhibitor: Galantamine HBr

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Product

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Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSⁿand 2D-NMR