A system suitability testing platform for untargeted, high-resolution mass spectrometry

Area of Science:

• Analytical Chemistry
• Metabolomics
• Mass Spectrometry

Background:

• Untargeted metabolomics faces challenges in harmonizing measurements over time due to the chemical complexity of samples.
• Internal isotopic standards are insufficient for normalizing untargeted metabolomics data post-analysis.
• Verifying instrument performance prior to sample injection is crucial for reliable data.

Purpose of the Study:

• To develop and evaluate a system suitability testing (SST) platform for time-of-flight mass spectrometers (TOF-MS) independent of liquid chromatography.
• To establish a method for a priori verification of instrument performance in untargeted metabolomics.

Main Methods:

• A chemically defined quality control mixture was used with a fast acquisition method.
• Software was developed to extract approximately 3,000 numerical features from profile data.
• A web service was implemented for monitoring instrument performance over a 21-month pilot study.

Main Results:

• The SST platform demonstrated effectiveness in detecting anomalies in instrument performance.
• Causal relationships between spectral features and machine settings were identified.
• Illustrative results showcase the potential for anomaly detection and performance monitoring.

Conclusions:

• The proposed SST platform provides a robust method for a priori instrument performance verification in untargeted metabolomics.
• The system enables anomaly detection, supports preventive maintenance, and offers features for future data harmonization.
• This approach addresses critical challenges in ensuring data quality and comparability in longitudinal metabolomics studies.