LAUSR

A new chemical labeling-based LC-MS/MS approach was developed for quantitative profiling of nine canonical bases and deoxynucleosides (dNs) in natural products. Using 2-bromo-1-(4-dimethylamino-phenyl)-ethaone (BrDPE) as the tagging reagent, a previously unexploited N-alkylpyrimidine derivative (Nad) was created for one-pot labeling of widescope nucleobases via a flexible bromophilic substitution under mild conditions. The derivatization notably improved the LC-MS detection sensitivity by 31-107 folds, enabling a fast dilute-and-shoot analysis of highly diluted samples. The optimized and validated method demonstrated satisfactory accuracy (87-107%), precision (RSDs<7.5%) and recovery (89-105%) for matrix-matched standard addition. The method was applied to simultaneously determine all target analytes and 4 uncanonical analogues and base-modified species in 7 traditional health foods, which differ in contents by up to 600-fold for discrimination among samples. Further, the base-labeled Nads exhibit a unique fragmentation signature that could be used for untargeted screening of nucleobase-containing metabolites by simplified LC-MS/MS workflow to improve quality evaluation of natural medicinal products.