1,4-Dioxo-1,2,3,4-tetrahydrophthalazine-6-carboxylic acid as a novel MALDI matrix for enhanced analysis of metabolites induced by imidacloprid exposure

Jingjing Yan; Wen Xie; Yingxue Jin; Zongwei Cai; Zian Lin

doi:10.1016/j.talanta.2025.127536

1,4-Dioxo-1,2,3,4-tetrahydrophthalazine-6-carboxylic acid as a novel MALDI matrix for enhanced analysis of metabolites induced by imidacloprid exposure

Talanta. 2025 Jan 4:286:127536. doi: 10.1016/j.talanta.2025.127536. Online ahead of print.

Authors

Jingjing Yan¹, Wen Xie¹, Yingxue Jin¹, Zongwei Cai², Zian Lin³

Affiliations

¹ Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
² State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon Tong, Hong Kong SAR, PR China. Electronic address: zwcai@hkbu.edu.hk.
³ Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China. Electronic address: zianlin@fzu.edu.cn.

PMID: 39765079
DOI: 10.1016/j.talanta.2025.127536

Abstract

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become a robust tool for analyzing a variety of biomacromolecules. However, the strong background interference produced by conventional organic matrices hinders the detection of small molecule analytes, which restricts the widespread application of MALDI-MS in metabolomics studies. Consequently, developing new organic matrices is urgently needed to overcome these issues. In this study, 1,4-Dioxo-1,2,3,4-tetrahydrophthalazine-6-carboxylic acid (DTCA) was firstly employed as a new matrix for MALDI-MS to enhance the detection of low molecular weight compounds because of its strong UV absorption, less matrix background interference, high ionization efficiency for metabolites, and good reproducibility. Considering these advantages, DTCA was used to analyze endogenous metabolites in the serum samples of imidacloprid (IMI)-exposed mice via MALDI-MS in positive ion mode. By combining with machine learning, the differentiation between imidacloprid-exposed mice and control mice was successfully achieved, and 39 metabolites were estimated as potential biomarkers. Additionally, potentially disrupted metabolic pathways were revealed. These results indicate that DTCA, as a new and powerful matrix in positive ion mode, has great potential for applications in the detection of small molecules.

Keywords: 1,4-Dioxo-1,2,3,4-tetrahydrophthalazine-6-carboxylic acid (DTCA); Imidacloprid exposure; MALDI-MS; Metabolic analysis.