Chemical and analytical characterization of related organic impurities in drugs

Gǒrög, Sándor

doi:10.1007/s00216-003-2140-6

Cited by 50 publications

(3 citation statements)

References 35 publications

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“…Preparation of small molecules of pharmaceutical interest can result in low molar fraction impurities that stem from unreacted starting materials or intermediates, products from competing side reactions and degraded or modified catalysts. 1–3 Because these diverse minor components may have unintended metabolic effects, impurities must be quantified and if present in sufficient molar excess, removed or structurally identified and shown to be biologically inert. 1–3 In proteomics, protein modifications can be indicative of biological activity as well as provide biomarkers for disease.…”

Section: Introductionmentioning

confidence: 99%

“…1–3 Because these diverse minor components may have unintended metabolic effects, impurities must be quantified and if present in sufficient molar excess, removed or structurally identified and shown to be biologically inert. 1–3 In proteomics, protein modifications can be indicative of biological activity as well as provide biomarkers for disease. 4–8 Quantitation of these discrete modifications can be used to determine relative expression levels in living systems.…”

Section: Introductionmentioning

confidence: 99%

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Direct Quantitation of Peptide Mixtures without Standards Using Clusters Formed by Electrospray Ionization Mass Spectrometry

2009

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In electrospray ionization mass spectrometry, ion abundances depend on a number of different factors, including analyte surface activity, competition between analytes for charge, analyte concentration, as well as instrumental factors, including mass-dependent ion transmission and detection. Here, a novel method for obtaining quantitative information about solution-phase concentrations of peptide mixtures is described and demonstrated for five different peptide mixtures with relative concentrations ranging from 0.05% to 50%. In this method, the abundances of large clusters containing anywhere from zero to thirteen impurity molecules are measured and directly related to the relative solution-phase concentration of the peptides. For clusters containing ~15 or more peptides, the composition of the clusters approaches the statistical value indicating that these clusters are formed nonspecifically and that any differences in ion detection or ionization efficiency are negligible at these large cluster sizes. This method is accurate to within ~20% or better, even when the relative ion intensities of the protonated monomers can differ by over an order of magnitude compared to their solution-phase concentrations. Although less accurate than other quantitation methods that employ internal standards, this method does have the key advantages of speed, simplicity, and the ability to quantitate components in solution even when the identity of the components are unknown.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Direct Quantitation of Peptide Mixtures without Standards Using Clusters Formed by Electrospray Ionization Mass Spectrometry

2009

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“…[1][2][3][4][5][6][7] The impurities present in API can be process impurities, degradation impurities or impurities originating from raw materials used in the synthesis. [8][9][10][11] The structural elucidation of an unknown impurity is a complex procedure. The conventional approach to the impurity identification consists of separation of the impurity from the main component followed by isolation and multiple spectroscopic analysis and/or analysis by other standard techniques such as x-ray crystallography and mass spectrometry (MS) of the isolated impurity.…”

Section: Introductionmentioning

confidence: 99%

Rapid Identification of Unknown Impurities in 3-Bromo-5-(trifluoromethyl)aniline by LC-SPE/NMR

Harča¹,

Habinovec²,

Meštrović³

et al. 2016

Croat. Chem. Acta

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Identification of unknown pharmaceutical impurities is an essential part in the drug development process. In the present study, we developed and applied liquid chromatography (LC)-solid-phase extraction (SPE) / nuclear magnetic resonance (NMR) methodology with cryoprobe for identification and structural characterization of unknown impurities in 3-bromo-5-(trifluoromethyl)aniline. The three main impurities were separated and isolated by LC-SPE system. After multiple trapping, isolated impurities were eluted from the SPE cartridges with deuterated acetonitrile and one-and two-dimensional homo-and heteronuclear NMR spectra were recorded. The structures of the unknown impurities were determined by detailed inspection of NMR spectra and by mass spectrometric (MS) analysis. The results of the present preliminary study demonstrated that LC-SPE/NMR can be used for rapid impurity profiling of 3-bromo-5-(trifluoromethyl)aniline.

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A Systematic Approach to Impurity Identification

Martin¹

2007

Analysis of Drug Impurities

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Chemical and analytical characterization of related organic impurities in drugs

Cited by 50 publications

References 35 publications

Direct Quantitation of Peptide Mixtures without Standards Using Clusters Formed by Electrospray Ionization Mass Spectrometry

Direct Quantitation of Peptide Mixtures without Standards Using Clusters Formed by Electrospray Ionization Mass Spectrometry

Rapid Identification of Unknown Impurities in 3-Bromo-5-(trifluoromethyl)aniline by LC-SPE/NMR

A Systematic Approach to Impurity Identification

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