Shotgun lipidomics is a powerful analytical technique that utilizes electrospray ionization mass spectrometry (ESI/MS) to analyze and quantify cellular lipidomes directly from crude extracts of biological samples. This method bypasses the need for prior chromatographic separation, allowing for the direct infusion of lipid extracts into the mass spectrometer. The technique leverages the intrinsic electrical properties of lipid classes to achieve intrasource separation, enabling the identification and quantification of a wide range of lipid species. This approach is particularly advantageous for its high throughput and comprehensive coverage, making it suitable for large-scale lipidomic studies Han, 2005.

One of the key strengths of shotgun lipidomics is its ability to perform multidimensional mass spectrometry and computer-assisted array analysis. This allows for the detailed characterization of lipid molecular species, including the discrimination of isobaric and isomeric species. The method’s high dynamic range and sensitivity enable the detection and quantification of low-abundance lipids, which is crucial for understanding lipid-mediated disease mechanisms. The technique’s robustness and reproducibility make it a valuable tool for clinical applications and biomarker discovery, as it can handle complex biological samples such as blood plasma with high precision Han, 2005; Surma, 2015.

Despite its advantages, shotgun lipidomics faces certain limitations, such as ion suppression and the generation of ion source artifacts, which can affect the accuracy of lipid identification and quantification. To address these challenges, various strategies have been developed, including the use of chemical derivatization, prefractionation, and the addition of modifiers to improve ionization efficiency. These enhancements have significantly improved the method’s accuracy and effectiveness, allowing for more comprehensive lipidomic analyses. As a result, shotgun lipidomics has become an indispensable tool for studying lipid metabolism and its alterations in health and disease Hu, 2020.

In summary, shotgun lipidomics is a high-throughput, comprehensive technique that uses ESI/MS for the direct analysis of lipidomes from crude biological extracts. It excels in multidimensional mass spectrometry and computer-assisted analysis, enabling detailed lipid characterization and quantification. Despite some limitations, recent advancements have enhanced its accuracy and utility, making it a crucial tool in lipidomics research and clinical applications.

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