Interplatform comparison between three ion mobility techniques for human plasma lipid collision cross sections

Area of Science:

• Analytical Chemistry
• Metabolomics
• Spectrometry

Background:

• Ion mobility spectrometry (IMS) coupled with liquid chromatography-high-resolution mass spectrometry (LC-HRMS) improves metabolomics compound annotation.
• Collision cross section (CCS) is a valuable molecular descriptor, but standardized protocols for its determination are lacking.
• Limited studies exist on interplatform agreement for CCS, especially for complex biological samples like plasma lipids.

Purpose of the Study:

• To compare collision cross section (CCS) values for approximately 100 lipid species across three different ion mobility technologies (DTIMS, TWIMS, TIMS).
• To evaluate instrument repeatability and interlaboratory reproducibility of CCS measurements.
• To assess the potential of CCS as a reliable molecular descriptor for human plasma lipids.

Main Methods:

• Comparison of CCS values for commercially available and human plasma-extracted lipids using drift tube IMS (DTIMS), travelling wave IMS (TWIMS), and trapped IMS (TIMS).
• Evaluation of eleven CCS calibrants, including ESI Low concentration tuning mix (Tune Mix).
• Analysis of data processing software impact on CCS discrepancies and assessment of interplatform correlation and reproducibility.

Main Results:

• Average CCS discrepancies of 0.3% were observed, influenced by data processing software.
• ESI Low concentration tuning mix (Tune Mix) showed the lowest relative standard deviation (< 0.5%) for CCS calibration across all instruments and ion modes.
• Over 90% of lipid CCS values showed deviations less than 1% between techniques, with high correlation (R² > 0.995) and reproducibility (mean RSD ≤ 1%) when using Tune Mix calibration.

Conclusions:

• High comparability and reproducibility of CCS determination for human plasma lipids are achievable across different IMS technologies.
• Standardized procedures for calibration, data acquisition, and processing are crucial for interplatform reproducibility.
• Harmonized analytical conditions are essential for reliable CCS determination and its use as a molecular descriptor in metabolomics.