Critical practical aspects in the application of liquid chromatography–mass spectrometric studies for the characterization of impurities and degradation products

• Practical issues in application of multi-step strategy for the characterization of IMPs/DPs.
• Practical aspects of sample preparation, method development and instrument settings.
• Critical practical considerations in acquisition and interpretation of mass results.
• Establishing fragmentation pathways of drug and IMPs/DPs from mass results and their comparison.
• Confirmation of structures through mechanistic explanation.

Liquid chromatography–mass spectrometry (LC–MS) is considered today as a mainstay tool for the structure characterization of minor components like impurities (IMPs) and degradation products (DPs) in drug substances and products. A multi-step systematic strategy for the purpose involves high resolution mass and multi-stage mass studies on both the drug and IMPs/DPs, followed by comparison of their fragmentation profiles. Its successful application requires consideration of many practical aspects at each step. The same are critically discussed in this review.

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