Shared reference materials harmonize lipidomics across MS-based detection platforms and laboratories.

Area of Science:

• Clinical Chemistry
• Analytical Chemistry
• Biochemistry

Background:

• Quantitative mass spectrometry (MS) of human plasma lipids is crucial for clinical applications.
• Current lipidomic methods, including direct infusion (DI) and liquid chromatography (LC), face challenges in standardization.
• Inter-laboratory variations in lipid measurements hinder the clinical use of lipid markers due to inconsistent reference values.

Purpose of the Study:

• To systematically investigate variables affecting quantitative lipid analysis in human plasma.
• To evaluate the impact of different sample introduction methods, MS instruments, and inter-laboratory differences.
• To identify strategies for harmonizing lipidomic data and establishing reliable reference values.

Main Methods:

• Analysis of human plasma samples from healthy adults using multiple quantitative MS approaches.
• Comparison of direct infusion (DI) versus chromatographic separation (reversed-phase and HILIC) methods.
• Assessment of variations across different MS instruments and between laboratories using comparable platforms.
• Inclusion of isotope-labeled internal standards for individual lipid classes.

Main Results:

• Significant quantitative differences were observed across various sample introduction methods, MS instruments, and laboratories.
• These discrepancies persisted even when using isotope-labeled internal standards.
• Normalization using commonly available shared reference samples effectively corrected systematic, method-specific quantitative biases.

Conclusions:

• Method-specific variables significantly impact quantitative lipidomic results in human plasma.
• Normalization to shared reference samples, like NIST SRM 1950, is essential for data harmonization.
• Complementing in-house references with shared reference materials will improve the reliability and comparability of lipidomics data in laboratory medicine.