Optimized LC-MS/MS approach for trace detection of trans-4,5-epoxy-(E)-2-decenal: Advancing volatile organic compounds biomarker research in human

Abstract

Volatile organic compounds (VOCs) play a critical role in human physiology, with their concentrations serving as key indicators of physiological states. Among these, trans-4,5-epoxy-(E)-2-decenal, a volatile organic compound found in mammalian blood, exhibits unique chemical reactivity and olfactory sensitivity due to its molecular structure, which is closely associated with lipid peroxidation processes. However, conventional detection methods, such as gas chromatography-olfactometry-mass spectrometry (GC-O-MS), suffer from limitations including inherent subjectivity, poor reproducibility, stringent operational requirements, and low throughput, which undermine their clinical reliability. To address these challenges, this study developed an optimized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for accurate qualitative and quantitative analysis. Given the poor detectability of aldehydes via LC-MS/MS, 2,4-dinitrophenylhydrazine (DNPH) derivatization was employed to enhance the chromatographic behavior and retention of the target compound. Additionally, HLB solid-phase extraction (SPE) columns was employed for purification to enhance the sensitivity of LC-MS/MS for the detection of trans-4,5-epoxy-(E)-2-decenal. Following derivatization, trans-4,5-epoxy-(E)-2-decenal demonstrated strong retention during chromatographic separation. The mobile phase, composed of acetonitrile and ultrapure water, exhibited significantly superior performance compared to combinations of acetonitrile with ammonium acetate buffer. Under optimized conditions, the LC-MS/MS method demonstrated excellent linearity for trans-4,5-epoxy-(E)-2-decenal within a range of 1–300 ng/mL, with correlation coefficient (R²) of 0.9984, detection limit (LOD) of 0.3 ng/mL. The relative standard deviation (RSD) for spiked blood samples in the experiment was 12.53 %.