Sample Preparation for Rapid Lipid Analysis in <em>Drosophila</em> Brain Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging

Phospholipidomics in Clinical Trials for Brain Disorders: Advancing our Understanding and Therapeutic Potentials

“… - Matrix interference for small lipid species. The presence of interfering matrix ion peaks below 800 Da interferes with the detection of small molecules - Limited for small, volatile lipids - MALDI-MS is primarily designed for solid and liquid samples and may not be suitable for analyzing gaseous samples [ 141 – 143 ] QQQ-MS (triple quadrupole MS) Involves the use of three quadrupole mass analyzers arranged in series to selectively filter ions based on their mass-to-charge ratios, allowing for precise quantification and structural elucidation of target analytes (such as lipids) in complex mixtures - Precise and quantitative lipid analysis including lipid class separation and species identification - It can differentiate between multiple analytes, even when they have similar mass-to-charge ratios - Excellent sensitivity for lipid quantitation - QQQ-MS is less susceptible to matrix effects compared to some other mass spectrometry techniques - Limited structural information.ires specific lipid standards for quantification - Expensive to purchase, complex setup, operate, and maintain - Developing robust and optimized QQQ-MS methods can be time-consuming and may require significant effort - QQQ-MS may struggle to differentiate between structural isomers, as their mass-to-charge ratios may be identical [ 144 , 145 ] LC-MS (liquid chromatography–mass spectrometry) Combines liquid chromatography with mass spectrometry for separation and analysis of lipid classes - Separation and identification of diverse lipid species - Highly sensitive and capable of detecting and quantifying compounds at very low concentrations - Modern LC-MS instruments offer high mass accuracy and resolution - Suitable for accurate determination of molecular weights and the identification of complex molecules - Can cover broad lipid coverage and is suitable for quantitative lipidomics - LC-MS instruments can be complex and require expertise for operation, maintenance, and data analysis - susceptible to matrix effects - - preparation involves a series of extraction and purification steps, which can lead to the use of toxic organic compounds - Some LC-MS instruments may have a limited mass range, which can restrict their applicability for high-mass or very low-mass compounds. - Method development is laborious and requires extensive optimization to achieve reliable and reproducible results [ 106 , 146 , 147 ] MS/MS (tandem mass spectrometry) Employs two or more mass analyzers in series for structural elucidation and quantification of lipids - Structural characterization of lipid species - High sensitivity for lipid identification - Enhanced specificity compared to single-stage mass spectrometry techniques - MS/MS is less susceptible to matrix effects compared to other MS - Suitable for the detection of trace-level compounds even in the presence of high-abu...…”