Profiling of aldehyde-containing compounds by stable isotope labelling-assisted mass spectrometry analysis

Abstract

We developed a strategy for non-targeted profiling of aldehyde-containing compounds by stable isotope labelling in combination with liquid chromatography-double neutral loss scan-mass spectrometry (SIL-LC-DNLS-MS) analysis. A pair of stable isotope labelling reagents (4-(2-(trimethylammonio)ethoxy)benzenaminium halide, 4-APC and d4-4-(2-(trimethylammonio)ethoxy)benzenaminium halide, 4-APC-d4) that can selectively label aldehyde-containing compounds were synthesized. The 4-APC and 4-APC-d4 labelled compounds were capable of generating two characteristic neutral fragments of 87 Da and 91 Da, respectively, under collision induced dissociation (CID). Therefore, double neutral loss scans were carried out simultaneously to record the signals of the potential aldehyde-containing compounds. In this respect, the aldehyde-containing compounds from two samples labelled with 4-APC and 4-APC-d4 were ionized at the same time but recorded separately by mass spectrometry. The peak pairs with characteristic mass differences (n × 4 Da) can be readily extracted from the DNLS spectra and assigned as potential aldehyde-containing candidates, which facilitates the identification of the target aldehydes. 4-APC and 4-APC-d4 labelling also dramatically increased detection sensitivities of the derivatives. Using the SIL-LC-DNLS-MS strategy, we successfully profiled the aldehyde-containing compounds in human urine and white wine. Our results showed that 16 and 19 potential aldehyde-containing compounds were discovered in human urine and white wine, respectively. In addition, 5 and 4 aldehyde-containing compounds in human urine and white wine were further identified by comparison with aldehyde standards. Altogether, SIL-LC-DNLS-MS demonstrated to be a promising approach in the identification and relative quantification of aldehyde-containing compounds from complex samples.

Sensitive mass spectrometric analysis of carbonyl metabolites in human urine and fecal samples using chemoselective modification

“…In total, we have validated 40 metabolites present in at least one of these three samples through co-injection experiments with these synthetic conjugate-standards. This number is higher than previous reports, 46 which stems from our method separating the captured metabolites from the matrix as well an increase in mass spectrometric sensitivity by several orders-ofmagnitude. Of these compounds, 35 have been reported previously in human samples according to the Human Metabolome Database (HMDB).…”

Lipoxidation in cardiovascular diseases

“…cytochrome c oxidase subunit I) [161,305]Platelet-derivedgrowth factor receptor beta [272]Carnosine [283,286,288]Serine/threonine-protein kinase STK11 [309]Glutathione [260]Ether-a-go-go-related channels [310]Lipid peroxidation-derived aldehydesMDA Free MDA : Spectrophotometric methods (sample derivatization with TBA) [170,[172], [173], [174]] MDA-protein adducts : Spectrophotometric methods (sample derivatization with TBA, strong acids, hydrazine-based or non-hydrazine-based reagents) [171,180,183] LC-UV or LC-FD [176,177,180] LC-MS/MS (e.g. SRM/MRM MS or label-free ; sample derivatization with AIDA assay, 4-APC) [[186], [187], [188],194,195] GC-MS/MS (sample derivatization with hydrazine-based or non-hydrazine-based reagents) [178,179,190,191,196] CE-UV [193]Atherosclerosis [112]Coronary and peripheral artery disease [196,311]Aortic stenosis [265]Heart failure [312]Apolipoprotein B-100 (LDLs) [43]Apolipoprotein AI (HDLs) [313]Mitochondrial proteins [314]Carnosine [282,285]Lipid peroxidation-derived aldehydesACR Free ACR : Fluorescence methods (e.g. Skraup reaction with m-aminophenol, lanthanide probe) [202,204,205]LC-FD [206,208]LC-MS/MS (sample derivatization) [214] ACR-protein adducts : Immunochemical methods [209,…”

Bioanalytical and Mass Spectrometric Methods for Aldehyde Profiling in Biological Fluids

“…This strategy enables profiling of 16 and 19 aldehyde-containing compounds in human urine and white wine, respectively. Finally, five aldehydes in human urine and four aldehydes in white wine are confirmed by comparison with synthetic standards [219]. This approach was further extended using an enrichment step by solid phase-extraction using stable isotope labeling–solid phase extraction–liquid chromatography–double precursor ion scan/double neutral loss scan–mass spectrometry analysis (SIL-SPE-LC-DPIS/DNLS-MS) for profiling and relative quantitation of aldehydes in beer.…”