A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

Singh, Saranjit; Handa, Tarun; Narayanam, Mallikarjun; Sahu, Archana; Junwal, Mahendra; Shah, Ravi P.

doi:10.1016/j.jpba.2012.03.044

Cited by 177 publications

(102 citation statements)

References 211 publications

(218 reference statements)

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“…The importance of the characterization of drug impurities and degradation products has been outlined in a recent critical review of the use of modern sophisticated hyphenated analytical methods [29]. Mass spectrometry is one of the main analytical tools used for the characterization of drug impurities and degradation products and is certainly very suitable for nucleic acid studies and the analysis of oligonucleotides [30].…”

Section: Principles Of Approachmentioning

confidence: 99%

A Novel and Intuitive Method of Displaying and Interacting with Mass Difference Information: Application to Oligonucleotide Drug Impurities

Roussis

2015

J. Am. Soc. Mass Spectrom.

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Abstract.A new method is presented for determining relationships between components in complex analytical systems. The method uses the mass differences between peaks in high resolution electrospray ionization (ESI) mass spectra. It relates peaks that share common mass differences. The method is based on the fundamental assumption that peaks in the spectra having the same exact mass difference are related by the same chemical moiety/substructure. Moreover, the presence (or absence/loss) of the same chemical moiety from a series of molecules may reflect similarities in the mechanisms of formation of each molecule. The determined mass differences in the spectra are used to automatically differentiate the types of components in the samples. Contour plots and summary plots of the summed total ion signal as a function of the mass difference are generated, which form powerful tools for the rapid and automated determination of the components in the samples and for comparisons with other samples. For the first time, in this work a unique profile contour plot has been developed that permits the interactive interrogation of the mass range by mass difference data matrix to obtain valuable information about components that share a common mechanism of formation, and all possible mechanisms of formation linked to a selected precursor molecule. The method can be used as an additional and complementary method to the existing analytical methods to determine relationships between components in complex chemical systems.

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Section: Principles Of Approachmentioning

confidence: 99%

A Novel and Intuitive Method of Displaying and Interacting with Mass Difference Information: Application to Oligonucleotide Drug Impurities

Roussis

2015

J. Am. Soc. Mass Spectrom.

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“…Hence, the structural information obtained from NMR analysis combined with the molecular mass and the fragmentation profile obtained from LC-MS n enable an unequivocal structural elucidation of impurities, mainly for isomeric mixtures. 1 For the purpose of structural identification of the LPSF-PT-31 impurities, the mixture of impurities A and B was subsequently analyzed through LC-SPE-NMR. The chromatographic conditions were optimized in order to offer a sufficient chromatographic separation, which was able to trap the impurities A and B by their retention time in two different SPE cartridges.…”

Section: Structure Elucidation Of the Unknown Impurities By Lc-ms N Amentioning

confidence: 99%

“…Impurity A showed to be 3-(2,4-dichlorobenzyl) imidazolidine-2,4-dione (1) (Figure 6) and it was identified by extensive analyses of 1 Supplementary Information, Figures S3-S5). Two methylene hydrogens appearing as a singlet at d 4.67 (s, H-6) showed HMBC correlations with C-2 (d 158.7) and C-4 (d 171.7).…”

Section: Structure Elucidation Of the Unknown Impurities By Lc-ms N Amentioning

confidence: 99%

“…Directly attached to C-6, an aromatic ring with a 1'-2'-4' substitution pattern was assigned. The NMR signal of H-3' appeared as a doublet at Considering impurity B, a good quality spectrum with sufficient signal-to-noise and resolution in a reasonable amount of time was not obtained for 1 13 C HMBC correlation maps obtained for the mixture (containing impurities A and B) and those data obtained for impurity A. Based on these, the same imidizalidine-2,4-dione was assigned, but the difference lies in the substitution pattern of the aromatic system, which in this case led to a 3-(3,4-dichlorobenzyl)imidazolidine-2,4-dione (2) (Figure 6).…”

Section: Structure Elucidation Of the Unknown Impurities By Lc-ms N Amentioning

confidence: 99%

“…[1][2][3][4][5] Detecting, isolating and structurally identifying impurities in drug substances and pharmaceutical formulations have been demanded by various regulatory organizations such as the Food and Drug Administration (FDA), 6 the International Conference on Harmonisation (ICH), 7 the European Medicines Agency (EMEA) 8 and the Brazilian Health Surveillance Agency (ANVISA). 9 Impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating drugs, but they can also be related to starting materials, byproducts, breakdown products or polymorphs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preparative Separation and Structural Identification of Impurities of a New α2‑Adrenoceptor Agonist Using Stacking Injection, LC-MSn and LC-SPE-NMR

Cardoso

Thomasi

Venâncio

et al. 2016

J. Braz. Chem. Soc.

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Identifying impurities in drug substances has become one of the most important issues in pharmaceutical analysis since it can have a significant impact on the efficacy of new pharmaceutical products. Due to the purity requirements, in this paper a new synthetic α 2 -adrenoceptor agonist, called LPSF-PT-31, was purified and its impurities were characterized by liquid chromatographymultistage mass spectrometry (LC-MS n ) and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR). The purification step was conducted using a semi-preparative liquid chromatography and stacked injections as a new approach to drug purification. As a result, a total yield of 75% of the pure LPSF-PT-31 and 2.9 L day -1 in solvent reduction was obtained. The combination of semi-preparative stacking injection, LC-MS n , and LC-SPE-NMR, demonstrated to be efficient to purify active drugs and unambiguously identify its impurities. In addition, isolation and identification of drug impurities in the early stages of development can improve the synthetic pathway, preventing the formation of impurities or minimizing this formation to minimum levels.

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Hyphenated Methods for Speciation Analysis

Michalski¹

2019

Encyclopedia of Analytical Chemistry

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Speciation analysis, understood as research into various element forms, is gaining importance in environment protection; biogeochemical cycles of chemical compounds; determination of toxicity and ecotoxicity of selected elements; quality control of food, medicines, and pharmaceutical products; examination of occupational exposure and clinical analysis. The hyphenated methods, in which separation method is coupled with multidimensional detectors, have become very useful in such analyses. The main advantages of those methods consist in extremely low detection and quantification limits, insignificant interference influence as well as high precision and repeatability of the determinations. The following article describes the role and importance of hyphenated methods in speciation analyses of selected elements.

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A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

Cited by 177 publications

References 211 publications

A Novel and Intuitive Method of Displaying and Interacting with Mass Difference Information: Application to Oligonucleotide Drug Impurities

A Novel and Intuitive Method of Displaying and Interacting with Mass Difference Information: Application to Oligonucleotide Drug Impurities

Preparative Separation and Structural Identification of Impurities of a New α2‑Adrenoceptor Agonist Using Stacking Injection, LC-MSn and LC-SPE-NMR

Hyphenated Methods for Speciation Analysis

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