Identification, isolation and characterization of potential process-related impurity and its degradation product in vildagliptin

Kumar, Neeraj; Devineni, Subba Rao; Singh, Gurmeet; Kadirappa, A.; Dubey, Shailendra Kumar; Kumar, Pramod

doi:10.1016/j.jpba.2015.11.044

Cited by 20 publications

(12 citation statements)

References 15 publications

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“…Therefore, the synthesis of impurities is not an easy task for the development team since the synthesis approach is not known or described in the literature. Our group has documented well the impurity profiling of vildagliptin, ticagrelor, acrivastine and clobazam including the synthesis of impurities [15] , [16] , [17] , [18] . However, extensive literature search disclosed that no liquid chromatography methods have been developed so far for the identification of impurities in isoproterenol hydrochloride.…”

Section: Introductionmentioning

confidence: 92%

“…Therefore, process development of the drug molecules without impurity profiling is scant and will be a challenging task for organic chemists. Many reports displayed the approach for the identification and characterization of unknown impurities formed in the drug development process [15] , [16] . In addition, some of the impurities are not available readily and would be essential in required quantity for method development and validation.…”

Section: Introductionmentioning

confidence: 99%

“…Considering the overview facts and our continuing efforts on impurity profiling [15] , [16] , [17] , [18] , considerable attention has been focused on identifying and characterizing the unknown impurity in isoproterenol hydrochloride by analytical applications. In addition, the new impurity, Imp-II was prepared by chemical synthesis with purity by avoiding tedious work-up procedure and laborious column chromatography techniques to use as a reference standard in analytical method development.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR

Kumar

Devineni

Gajjala

et al. 2017

Journal of Pharmaceutical Analysis

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One unknown impurity (Imp-II) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol (Imp-II) using the liquid chromatography--mass spectrophotometry (LC--MS) analysis. Imp-II was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C, DEPT (1D NMR), HSQC (2D NMR) and infrared spectroscopy (IR), and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification, the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit<0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR

Kumar

Devineni

Gajjala

et al. 2017

Journal of Pharmaceutical Analysis

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“…FT-IR, NMR (1H, 13C and DEPT), 2D NMR (HSQC, HMBC and COSY) and mass spectral data (8aS)-3-hydroxyoctahydropyrrolo[1,2-a]piperazine-1,4-dione (Impurity-F) were used to determine the structure of stable impurity. Impurity detection, unusual impurity-E behaviour, impurity-F isolation, fragmentation mechanism and structural elucidation were also addressed (Kumar et al, 2016).…”

Section: Pro Iling Of Impurities By Hplc and 2d Nmrmentioning

confidence: 99%

Innovative methodologies for identification and qualification of Impurities: An overview of the latest trends on impurity profiling

Nishanth¹,

Akhila²,

Tengli³

et al. 2020

ijrps

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Impurity profiling is known to identify, classify and measure both the identified and non-identified contamination present on the medicinal product. Unwanted chemicals which remain or are created during the formulation of medicinal products are pharmaceutical impurities. Impurity profiling helps in the detection, recognition and quantification in bulk products and pharmaceutical formulations of various types of impurities, as well as residual solvents. It is the simplest way to distinguish consistency and stability of bulk drugs and medication formulations. As analytical methodology has developed rapidly, it is essential to consider with their solutions problems related to impurities of drug substances and drug products. Various regulatory agencies including ICH, USFDA, Canadian Drug and Health Agencies stress the criteria for purity and for detecting impurities in active pharmaceutical materials, even in small quantities, as the presence of impurities, may have an effect on pharmaceutical products ’ efficacy and health. Therefore, the study focuses on various analytical methods for identification and quantification of impurities in pharmaceutical products to clarify the need for impurity profiling on drug products in pharmaceutical research. To drug regulators, the product substance’s impurity profile is a reliable fingerprint to prove that the manufacturing process of bulk drug substances is consistent in quality. The study gives a short summary of recent technical developments in the profiling of pharmaceutical products including pharmaceutical active ingredients as well as pharmaceutical products during 2013-2017. Such recent trends in the profiling of impurities have been addressed in the study. This focuses specifically on a thorough update on various analytical techniques, including hyphenated methods to define and measure thresholds in specific pharmaceutical matrices of impurities and degradants.

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“…Continuing our interest in the process research and development of API [[25], [26], [27], [28]] and their impurity profiling [[29], [30], [31]] as a means of pharmaceutical analysis to manufacture high quality drug, herein, we report our investigation towards the formation and control of potential dimer impurity E ( 1 ) in the synthesis of PAN, and a most optimal preparation procedure of dimer impurity. The data obtained will facilitate the optimization of manufacturing processes and the quality control of PAN.…”

Section: Introductionmentioning

confidence: 99%

Prospects to the formation and control of potential dimer impurity E of pantoprazole sodium sesquihydrate

Awasthi

Kumar

Tripathi

et al. 2019

Journal of Pharmaceutical Analysis

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Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) specify six impurities, viz. ; impurities A, B, C, D, E and F, respectively for its active pharmaceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature; however, there is no report related to impurity E. The prospects to the formation and controlling of impurity E up to ≤0.03% in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.

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Identification, isolation and characterization of potential process-related impurity and its degradation product in vildagliptin

Cited by 20 publications

References 15 publications

Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR

Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR

Innovative methodologies for identification and qualification of Impurities: An overview of the latest trends on impurity profiling

Prospects to the formation and control of potential dimer impurity E of pantoprazole sodium sesquihydrate

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