Recent studies on the electrospray ionisation mass spectrometric behaviour of selected nitrogen-containing drug molecules and its application to drug analysis using liquid chromatography–electrospray ionisation mass spectrometry

Wf, Smyth

doi:10.1016/j.jchromb.2005.07.018

Cited by 50 publications

(24 citation statements)

References 66 publications

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“…Other examples where MS 2 fragmentation leads to cleavage of a C-N bond with amine release are mostly found for tertiary amines, as these have C-N bond dissociation energies (BDE) lower than those of their secondary amine counterparts [31]. For instance, the ESI-MS behavior of therapeutically relevant tertiary amines has been described by Smyth and co-workers to involve fragmentation to smaller amines [34,47], as nicely reviewed in [31]. Amine release is also common in MS 2 fragmentations of oligopeptides, though through different pathways, as for instance the y 7 fragmentation of the bioactive octapeptide Angiotensin II, corresponding to loss of the N-terminal Asp residue as 3-aminodihydrofuran-2,5-dione.…”

Section: Esi-ms 2 Analysis At Varying Nce Valuesmentioning

confidence: 99%

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Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

Vale

Moreira

Gomes

2008

International Journal of Mass Spectrometry

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The extensive characterization by electrospray ionization-ion trap mass spectrometry (ESI-MS n ) of 20 imidazolidin-4-ones derived from the antimalarial primaquine was well obtained. These compounds are being under investigation as potential antimalarials, as they have been previously found to be active against rodent P. berghei malaria and to be highly stable under physiological conditions. Experiments by collision-induced dissociation (CID) in the nozzle-skimmer region or by tandem-MS have shown the title compounds to be remarkably stable. Mechanisms are proposed to explain the major fragmentations observed in ESI-MS n experiments. Overall, this work represents an unprecedented contribution to a deeper insight into imidazolidin-4-one antimalarials based on a classic 8-aminoquinolinic scaffold. Data herein reported and discussed may be an useful guide for future studies on therapeutically relevant molecules possessing either the 8-aminoquinoline or the imidazolidin-4-one motifs.

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Section: Esi-ms 2 Analysis At Varying Nce Valuesmentioning

confidence: 99%

“…to time-of-flight mass spectrometry (ToF-MS) [31,32,35]. ESI-MS n studies of antimalarial compounds as bisthiazolium or quinolines can be found on reports by Nicolas et al [38] or Smyth et al and O'Donnell et al [34,39], respectively.…”

Section: Introductionmentioning

confidence: 99%

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

Vale

Moreira

Gomes

2008

International Journal of Mass Spectrometry

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“…This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1-3] to synthetic drugs [4-8], peptides [9-23], and heterocycles [24][25][26][27][28], among many others. Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures.…”

confidence: 99%

“…Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the O ver the past decade, electrospray ionization mass spectrometry (ESI-MS) has been used for the most diverse analytical purposes. This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1][2][3] to synthetic drugs [4][5][6][7][8], peptides [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], and heterocycles [24][25][26][27][28], among many others. Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures.…”

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confidence: 99%

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

Vale

Matos

Moreira

et al. 2008

J. Am. Soc. Mass Spectrom.

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Electrospray ionization-ion trap mass spectrometry (ESI-MS) of imidazolidin-4-one peptidemimetic derivatives of the antimalarial drug primaquine (PQ) is reported. These compounds contain the imidazolidin-4-one moiety either at the N-or the C-terminal of a dipeptide backbone, thus respectively mimicking PQ-Amino Acid-Proline (PQAAPro) and PQProAA derivatives of PQ. Both the peptidomimetics and precursors previously developed by us are promising drug candidates, as they were found to be active against rodent Plasmodium berghei malaria and Pneumocystis carinii pneumonia. Collision-induced dissociation (GD) and tandemmass spectra (MS) of the title compounds, and fragmentation pathways thereof, led to the following findings: (1) CID patterns present some parallelism with the reactivity towards hydrolysis previously found for the same or related compounds; (2) a positional shift of the imidazolidin-d-one ring is reflected on both degree and pathways of fragmentation, which makes tandem-MS a key tool for differentiation of imidazolidin-i-one isomers; (3) the major MS/MS fragmentation of PQProAA mimetics involves release of a neutral diketopiperazine (DKP), in parallel to the "diketopiperazine pathway" described in tandem-MS studies of oligopeptides; (4) the relative abundance of a major fragment in tandem-MS spectra is inversely correlated with the size of the N-terminal AA in PQProAA mimetics. Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the 8-aminoquinoline and, especially, the imidazolidin-4-one structural classes. aAm Soc Mass Spectrom 2008, 19, 1476-1490 ) © 2008 American Society for Mass SpectrometryO ver the past decade, electrospray ionization mass spectrometry (ESI-MS) has been used for the most diverse analytical purposes. This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1-3] to synthetic drugs [4-8], peptides [9-23], and heterocycles [24][25][26][27][28], among many others. Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures. Analytical methods focused on PQ or its analogues have been so far applied to pharmacokinetics studies and metabolite scrutiny [29][30][31][32][33][34][35][36][37] or isomer characterization [38,39]. Examples of mass spectrometry techniques employed to the study/analysis of PQ and related compounds include fast atom bombardment mass spectral (FAB-MS) analysis of PQ oxidation products [32] and supercritical fluid chromatography-mass Address reprint requests to Dr. P.

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“…It is well known that phosphoric acid is a nonvolatile reagent and is not compatible with LC/MS analysis. For that reason, a new reagent (formic acid) suitable for LC/MS analysis was included and the method was developed [6][7][8][9][10].…”

Section: Hplc/msmentioning

confidence: 99%

Identification and Structural Characterization of Unidentified Impurity in Bisoprolol Film-Coated Tablets

Mitrevska

Kikovska-Stojanovska

Petruševski

et al. 2017

Advances in Chemistry

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The aim of this study is the identification, structural characterization, and qualification of a degradation impurity of bisoprolol labeled as Impurity RRT 0.95. This degradation product is considered as a principal thermal degradation impurity identified in bisoprolol film-coated tablets. The impurity has been observed in the stress thermal degradation study of the drug product. Using HPLC/DAD/ESI-MS method, a tentative structure was assigned and afterwards confirmed by detailed structural characterization using NMR spectroscopy. The structure of the target Impurity RRT 0.95 was elucidated as phosphomonoester of bisoprolol, having relative molecular mass of 406 (positive ionization mode). The structural characterization was followed by qualification of Impurity RRT 0.95 using several different in silico methodologies. From the results obtained, it can be concluded that no new structural alerts have been generated for Impurity RRT 0.95 relative to the parent compound bisoprolol. The current study presents an in-depth analysis of the full characterization and qualification of an unidentified impurity in a drug product with the purpose of properly defining the quality specification of the product.

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Recent studies on the electrospray ionisation mass spectrometric behaviour of selected nitrogen-containing drug molecules and its application to drug analysis using liquid chromatography–electrospray ionisation mass spectrometry

Cited by 50 publications

References 66 publications

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

Identification and Structural Characterization of Unidentified Impurity in Bisoprolol Film-Coated Tablets

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