Four process-related potential new impurities in ticagrelor: Identification, isolation, characterization using HPLC, LC/ESI–MSn, NMR and their synthesis

Kumar, Neeraj; Devineni, Subba Rao; Gajjala, Prasad Reddy; Gupta, Dharmendra K.; Bhat, Sandesh; Kumar, Rajesh; Dubey, Shailendra Kumar; Kumar, Pramod

doi:10.1016/j.jpba.2015.12.037

Cited by 18 publications

(7 citation statements)

References 14 publications

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“…The obtained samples were used for following spectral analysis, including MS, 1 D and 2 D NMR and IR for structural characterization of the compounds. A plausible mechanism for the formation of impurities was discussed; the unknown impurities were prepared synthetically with the purpose of being used as reference standards in analytical method development (Kumar, Devineni et al, ).…”

Section: Methodsmentioning

confidence: 99%

Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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Ticagrelor is an orally administered platelet aggregation inhibitor with a cyclopentyl‐triazolopyrimidine structure; it is a selective reversible P2Y12 receptor antagonist, which prevents P2Y12‐mediated and ADP‐mediated platelet activation and aggregation. It is used to reduce the rate of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome or history of myocardial infarction. Several analytical methods have been published for the determination of ticagrelor in pharmaceuticals and biological materials by spectrophotometry, high‐performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the determination of ticagrelor since its introduction in therapy until today.

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Section: Methodsmentioning

confidence: 99%

Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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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: 93%

“…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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“…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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Four process-related potential new impurities in ticagrelor: Identification, isolation, characterization using HPLC, LC/ESI–MSn, NMR and their synthesis

Cited by 18 publications

References 14 publications

Analytical methodologies for the determination of ticagrelor

Analytical methodologies for the determination of ticagrelor

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

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

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