Target and Semitarget Analysis of Advanced Glycation End Products Using a New Pair of Permanently Positively Charged Stable Isotope Labeling Agents

A pair of positively charged stable isotope labeling (SIL) agents, (4-carbonochloridoylphenyl)-trimethylazanium iodide (d₀-CCPTA) and d₆-CCPTA, were designed and synthesized. These agents were employed in the precolumn labeling of advanced glycation end products (AGEs) within 5 min under mild conditions. Through derivatization, the mass spectrometry response of the AGEs was enhanced by approximately 2 orders of magnitude. The detection and quantitation limits were in the ranges of 3.1–7.1 and 10.0–23.7 ng/kg, respectively. The recoveries were in the range of 90.1–94.3%, and the matrix effect ranged from −6.6 to −3.5%. CCPTA produced “CCPTA-specific production ions”, and all analytes were analyzed by common multiple reaction monitoring (MRM) parameters. The common MRM parameters were applied to the semitarget analysis of 41 types of AGE candidates in the absence of standards, with 13 AGEs identified.