Available online 13 February 2023

DIPP derivatization-chip 2D LC-QQQ/MS was developed to sensitively quantify TAs.

Sensitivities increased up to 5520 times compared with nonderivatization-UHPLC-QQQ/MS.

The lowest LOQ reached to 1 pg/mL level.

Phenylalanine and tyrosine metabolic pathways were closely related to sorafenib treatment.

Trace amines (TAs) are metabolically related to catecholamine and associated with cancer and neurological disorders. Comprehensive measurement of TAs is essential for understanding pathological processes 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 simultaneously 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.

Chip 2D LC-QQQ/MS

Trace amines

Derivatization

Hepatoma

© 2023 The Author(s). Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.