학술논문
Identification, isolation, characterization and response factor determination of process-related impurity in meprobamate drug substance.
Document Type
Academic Journal
Author
Karthikeyan K; Shasun Research Center, 27, Vandalur Kelambakkam Road, Keelakottaiyur, Chennai 600048, India. karthikeyan@shasun.com; Arularasu GT; Murali V; Pillai KC
Source
Publisher: Elsevier Science Country of Publication: England NLM ID: 8309336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-264X (Electronic) Linking ISSN: 07317085 NLM ISO Abbreviation: J Pharm Biomed Anal Subsets: MEDLINE
Subject
Language
English
Abstract
This paper describes identification and characterization of a process-related impurity of meprobamate drug substance observed in HPLC-UV method. Forced degradation studies were carried out under acidic, basic, oxidation, light and thermal conditions to assess the nature of the impurity. The pure impurity was obtained by preparative LC isolation and analyzed by NMR and mass. Structural elucidation by spectral data and formation of this impurity were discussed in detail. The structure of the process-related impurity was established as carbamic acid-2-carbamoyloxymethyl-2-methyl-pent-3-enyl ester (olefin). Also, the relative response factor, linearity, detection limit (DL), quantitation limit (QL) and recovery were determined for meprobamate and the impurity. Good linearity was obtained for the impurity over the concentration range of 0.03-0.20% (w/w) with the coefficient of determination (r(2)) of 0.999. The DL and QL of olefin impurity were 0.0003 and 0.001% (w/w), respectively. The isolated impurity was co-injected with meprobamate sample to confirm the retention time in HPLC.
(Copyright © 2010 Elsevier B.V. All rights reserved.)
(Copyright © 2010 Elsevier B.V. All rights reserved.)