Tutorial review on validation of liquid chromatography-mass spectrometry methods: part I

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Chromatography

Background:

• Method validation is crucial for reliable analytical results.
• Liquid chromatography-mass spectrometry (LC-MS) offers sensitive detection but presents unique validation challenges compared to conventional detectors.
• Existing guidelines need specific interpretation for LC-MS applications.

Purpose of the Study:

• To provide a state-of-the-art overview of method validation in LC-MS.
• To discuss specific validation issues pertinent to MS and MS/MS detection in LC.
• To offer recommendations for determining key performance parameters in LC-MS methods.

Main Methods:

• Review of operational principles of LC-MS, focusing on ionization processes and suppression/enhancement effects relevant to validation.
• Comprehensive review of major method validation guideline documents.
• Detailed discussion and recommendations for evaluating selectivity/specificity/identity, ruggedness/robustness, limit of detection (LOD), limit of quantification (LOQ), decision limit (CCα), and detection capability (CCβ).

Main Results:

• Clarification of terminology and current practices for essential validation parameters in LC-MS.
• Identification of specific challenges in LC-MS method validation, including ionization-related phenomena.
• Proposed approaches for determining performance characteristics tailored to LC-MS.

Conclusions:

• A clear understanding of validation principles and specific LC-MS issues is essential for robust method development.
• Standardized approaches to evaluating performance parameters are recommended for LC-MS applications.
• This review serves as a guide for researchers and practitioners in validating LC-MS methods.