Isotope-coded derivatization with designed Girard-type reagent as charged isobaric mass tags for non-targeted profiling and discovery of natural aldehydes by liquid chromatography-tandem mass spectrometry
Aldehyde-containing metabolites are reactive electrophiles that have attracted extensive attention due to their widespread occurrence in organisms and natural foods. Herein we described a newly-designed Girard's reagent, 1-(4-hydrazinyl-4-oxobutyl)pyridin-1-ium bromide (HBP), as charged tandem mass (MS/MS) tags to facilitate selective capture, sensitive detection and semi-targeted discovery of aldehyde metabolites via hydrazone formation. After HBP labeling, the detection signals of the test aldehydes were increased by 21–2856 times, with the limits of detection were 2.5–7 nM. Upon isotope-coded derivatization with a pair of labeling reagents, HBP- d 0 and its deuterium-labeled counterpart HBP- d 5 , the aldehyde analytes were converted to hydrazone derivatives, which generated characteristic neutral fragments of 79 Da and 84 Da, respectively. The isobaric HBP- d 0 /HBP- d 5 labeling based LC-MS/MS method was validated by relative quantification of human urinary aldehydes (slope=0.999, R 2 > 0.99, RSD s ≤ 8.5%) and discrimination analysis between diabetic and control samples. The unique isotopic doubles (Δ m/z = 5 Da) by dual neutral loss scanning (dNLS) provided a generic reactivity-based screening strategy that allowed non-targeted profiling and identification of endogenous aldehydes even amidst noisy data. The LC-dNLS-MS/MS screening of cinnamon extracts led to finding 61 possible natural aldehydes and guided discovery of 10 previously undetected congeners in this medicinal plant.
危险品化学品经营许可证（带存储）