Identification, synthesis and structural characterization of process related and degradation impurities of acrivastine and validation of HPLC method

Ajay Kumar, Subba Rao Devineni, Shailender Kumar Dubey, Pradeep Kumar, Vishal Srivastava, Girish Ambulgekar, Mohit Jain, Dharmendra Kumar Gupta, Gurmeet Singh, Rajesh Kumar, S. G. Hiriyanna, Pramod Kumar

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Four impurities (Imp-I–IV) were detected using gradient HPLC method in few laboratory batches of acrivastine in the level of 0.03–0.12% and three impurities (Imp-I–III) were found to be known and one (Imp-IV) was unknown. In forced degradation study, the drug is degraded into four degradation products under oxidation and photolytic conditions. Two impurities (Imp-III and -IV) were concurred with process related impurities whereas Imp-V and -VI were identified as new degradation impurities. Based on LC-ESI/MS n study, the chemical structures of new impurities were presumed as 1-[(2E)-3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}prop-2-en-1-yl]pyrrolidin-1-ium-1-olate (Imp-IV), 1-{[3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}oxiran-2-yl]methyl}pyrrolidin-1-ium-1-olate (Imp-V) and 2-[2-(4-methylphenyl)-3-[(1-oxidopyrrolidin-1-ium-1-yl)methyl]oxiran-2-yl]-6-[(1E)-3-oxobut-1-en-1-yl]pyridin-1-ium-1-olate (Imp-VI), and confirmed by their synthesis followed by spectroscopic analysis, IR, NMR ( 1 H, 13 C) and mass. An efficient and selective high-performance liquid chromatography method has been developed and resolved well the drug related substances on a Phenomenex Gemini C-18 (250 × 4.6 mm, particle size 5 μm) column. The mobile phase was composed of sodium dihydrogen phosphate (10 mM) and methanol, temperature at 25 °C, and a PDA detector set at 254 nm used for detection. The method was validated with respect to specificity, linearity, precision, accuracy, and sensitivity and satisfactory results were achieved. Identification, synthesis, characterization of impurities and method validation were first reported in this paper.

Original languageEnglish
Pages (from-to)15-26
Number of pages12
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume133
DOIs
StatePublished - 30 Jan 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V.

Keywords

  • Acrivastine
  • Characterization
  • Forced degradation
  • Identification
  • Impurities
  • Method validation

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