A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

J Pharm Biomed Anal. 2012 Oct;69:148-73. doi: 10.1016/j.jpba.2012.03.044. Epub 2012 Mar 30.

Abstract

With ever increasing regulatory and compendial stringency on the control of impurities (IMPs) and degradation products (DPs) (including genotoxic impurities) in drug substances and finished pharmaceutical formulations, a profound emphasis is being paid on their characterization and analysis at trace levels. Fortunately, there have been parallel tremendous advancements in the instrumental techniques that allow rapid characterization of IMPs and/or DPs at the prescribed levels of ∼0.1%. With this, there is perceptible shift from conventional protocol of isolation and spectral analysis to on-line analysis using modern sophisticated hyphenated tools, like GC-MS, LC-MS, CE-MS, SFC-MS, LC-NMR, CE-NMR, LC-FTIR, etc. These are already being extensively used by industry and also there is tremendous increase in publications in the literature involving their use. This write-up critically reviews the literature for application of hyphenated tools in impurity and degradation product profiling of small molecules. A brief mention is made on possible pitfalls in the experimentation and data interpretation. Appropriate strategies are proposed, following which one can obtain unambiguous characterization of the unidentified IMPs and/or DPs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chemistry, Pharmaceutical / methods
  • Chromatography, Gas / methods
  • Chromatography, Liquid / methods
  • Dose-Response Relationship, Drug
  • Drug Contamination*
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Hydrolysis
  • Magnetic Resonance Spectroscopy / methods
  • Mass Spectrometry / methods
  • Mutagens / chemistry*
  • Pharmaceutical Preparations / analysis*
  • Pharmaceutical Preparations / chemistry
  • Reproducibility of Results
  • Spectroscopy, Fourier Transform Infrared / methods
  • Technology, Pharmaceutical / methods

Substances

  • Mutagens
  • Pharmaceutical Preparations