Identification, Synthesis, Characterization and Quality Control Strategy of New Process-Related Impurities in Fosphenytoin Sodium-Reference-Cited by-同舟云学术

Identification, Synthesis, Characterization and Quality Control Strategy of New Process-Related Impurities in Fosphenytoin Sodium

Published:2020 Issue:8 Volume:32 Page:1881-1885
ISSN:0975-427X
Container-title:Asian Journal of Chemistry
language:en
Short-container-title:Asian J. Chem.

Author:

Singaram Sathiyanarayanan¹,Subramanian Venkatesan Chidambaram²,Kabilan Senthamaraikannan³,Suresh Raju Dandu Bhaskara²

Affiliation:

1. 1Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar-608002, India 2Gland Pharma Ltd., Research and Development, D.P. Pally, Hyderabad-500043, India

2. Gland Pharma Ltd., Research and Development, D.P. Pally, Hyderabad-500043, India

3. Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar-608002, India

Abstract

Fosphenytoin sodium is a water dissolvable phenytoin prodrug that is directed intravenously to convey phenytoin, conceivably more securely than intravenous phenytoin. It is most ordinarily utilized in the intense treatment of convulsive status epileptics. The examination of the procedure-related contaminants will not help exclusively to advance the process parameters yet additionally to create sensible analytical methods and set the quality standard for a quality control system in pharmaceutical manufacturing. During the production of fosphenytoin sodium, all the process-related impurities are controlled in every stage and three degradation impurities are managed in the final API as per USP monograph. Besides, five unknown and one known contaminants were detected by HPLC method. All these impurities were identified, synthesized, isolated and characterized by IR, 1D-NMR (1H, 13C, DEPT) and HRMS spectral techniques. The mechanism of the formed impurities is examined for the first time. Quality control procedures to manage these impurities were developed to acquire the mass medication of ICH grade quality.

Publisher

Asian Journal of Chemistry

Subject

General Chemistry

Reference9 articles.

1. Phenytoin Prodrugs III: Water-Soluble Prodrugs for Oral and/or Parenteral Use

2. E.M. Davis, J.E. Ellis and D.A. Katonak, Process for the Synthesis of Diesters of Phosphoric Acid 2,5-Dioxo-4,4-diphenyl-imidazolidin-1-ylmethyl Ester, US Patent 6022975A (2000).

3. K. Volker, Process for the Preparation of Sodium Fosphenytoin, US Patent 2005272706 (2005).

4. Novel Synthesis of Fosphenytoin: Anti-Convulsant Prodrug

5. Y. Duan, CN Patent 102060874A (2009).