Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

Amino-containing compounds,including amino acids,aliphatic amines,aromatic amines,small peptides and catecholamines,are involved in various biological processes and play vital roles in multiple meta-bolic pathways.Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer.However,the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need.Herein,we established a polarity-regulated derivatization method coupled with liquid chromatography-mass spectrometry(LC-MS)for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls,based on our newly designed and synthesized derivatization reagent(S)-3-(1-(diisopropox-yphosphoryl)pyrrolidine-2-carboxamido)-N-hydroxysuccinimidyl ester(3-DP-NHS).Enhanced separa-tion efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization.This method exhibited good linearity,recovery,intra-and inter-day precision and accu-racy.Only 5 μL serum is needed for untargeted analysis,enabling 202 amino-containing metabolites to be detected.Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer.Furthermore,ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS)analysis quantification revealed increased serum levels of tryptamine and decreased concen-trations of arginine and tryptophan in patients with gastric cancer.Receiver operating characteristic(ROC)curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis.This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis,providing new avenues for the treatment of gastric cancer.