Integrating Electrostatic Adsorption-Laser Desorption/Ionization-MS with a Derivative Full-Spectrum Internal Standard Approach for Acylcarnitine Quantification in Clinical Samples
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引用次数: 0
Abstract
Acylcarnitines (ACs), essential intermediates in fatty acid β-oxidation, are increasingly recognized as biomarkers for inborn errors of metabolism (IEM), insulin resistance, heart failure, and neurodegenerative diseases. However, conventional liquid chromatography–mass spectrometry (LC-MS) and flow injection–mass spectrometry (FI-MS) methods are hindered by complex sample preparation, limited throughput, and matrix interferences. Meanwhile, matrix-assisted laser desorption/ionization–MS (MALDI-MS) suffers from low-mass background noise and poor reproducibility. Here, we present a dual-innovation mass spectrometry platform combining a substrate composed of sulfonic acid–gold nanoparticle-decorated silicon nanowires (Sulfo-Au-SiNWs) for electrostatic adsorption-laser desorption/ionization (EALDI) and a full-spectrum internal standard (FS IS) strategy based on d6-ethanol derivatization. The optimized Sulfo-Au-SiNWs offer uniform crystallinity, in situ electrostatic enrichment, efficient thermal desorption, and gold-mediated charge–hole separation, resulting in a ∼300% increase in AC signal intensity. This enabled the selective detection of over ten medium- and long-chain ACs that were previously undetectable using unmodified SiNWs. The FS IS method incorporates over 30 derivatized AC species, enabling simultaneous quantification with detection limits below 0.01 μmol/L, surpassing the sensitivity of traditional FI-MS. The platform delivers spike recovery rates of 96–112% and supports high-throughput analysis, processing each sample within seconds. Validation against FI-ESI-MS/MS in both urine and dried blood spot samples demonstrated excellent agreement (ρ > 0.95) and effectively identified IEM patient profiles via statistically significant AC elevations. With strong intra- and interbatch precision (median RSD < 12.5%) and substrate stability exceeding one month, this EALDI-MS/FS IS workflow provides a high-throughput, high-coverage, and quantitatively robust solution for clinical AC profiling and newborn screening.
期刊介绍:
The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role.
Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives