Gas chromatography-mass spectrometry-based analytical strategies for fatty acid analysis in biological samples

Fatty acids play critical roles in biological systems. Imbalances in fatty acids are related to a variety of diseases, which makes the measurement of fatty acids in biological samples important. Many analytical strategies have been developed to investigate fatty acids in various biological samples. Due to the structural diversity of fatty acids, many factors need to be considered when developing analytical methods including extraction methods, derivatization methods, column selections, and internal standard selections. This review focused on gas chromatography-mass spectrometry (GC-MS)-based methods. We reviewed several commonly used fatty acid extraction approaches, including liquid-liquid extraction and solid-phase microextraction. Moreover, both acid and base derivatization methods and other specially designed methods were comprehensively reviewed, and their strengths and limitations were discussed. Having good separation efficiency is essential to building an accurate and reliable GC-MS platform for fatty acid analysis. We reviewed the separation performance of different columns and discussed the application of multidimensional GC for improving separations. The selection of internal standards was also discussed. In the final section, we introduced several biomedical studies that measured fatty acid levels in different sample matrices and provided hints on the relationships between fatty acid imbalances and diseases.