Chemical Stabilization and Retention-Predictive Modeling for Regiospecific Profiling of Labile Monoacylglycerols by UHPLC–HRMS
5 affiliations
- 1State Key Laboratory of Mechanism and Quality of Chinese Medicine, University of Macau, Macau SAR 999078, China
- 2Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China
- 3Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi, Shanxi 046000, China
- 4Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
- 5Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract
Regiospecific analysis of monoacylglycerols (MAGs) remains challenging because of their low endogenous abundance, the limited availability of regioisomeric standards, and rapid acyl migration between the sn-1 and sn-2 positions during sample handling. Here, we report an UHPLC–HRMS platform integrating chemical stabilization with retention-time prediction for confident profiling of MAG regioisomers in biological samples. Derivatization with 4-pyridineboronic acid (4-PyBA) selectively forms cyclic boronate esters with the glycerol cis-diol moiety, thereby suppressing acyl migration, enhancing electrospray ionization efficiency, and generating characteristic diagnostic ions. To minimize reliance on authentic standards, a three-dimensional quantitative structure–retention relationship (3D-QSRR) model was developed to predict chromatographic retention across structurally diverse MAGs. In parallel, a homologous series of fatty acid 1,2-pentanediol monoesters was synthesized as retention calibrants to correct retention time (RT) drift and improve method robustness. These components were integrated into a targeted parallel reaction monitoring (PRM) workflow supported by an in-house database of 288 annotated sn-1 and sn-2 MAGs. Application of this strategy to serum, brain, colon, and fecal samples from APP/PS1 mice and to serum samples from individuals with Alzheimer’s disease (AD) enabled the confident annotation of 118 endogenous MAGs, including 68 MAGs not currently catalogued in major public databases. Collectively, this integrated platform improves structural confidence and analytical robustness and establishes a transferable framework for regioisomer-resolved analysis of labile glycerolipids.
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BibTeX
@article{zhou2026chemical,
title = {{Chemical Stabilization and Retention-Predictive Modeling for Regiospecific Profiling of Labile Monoacylglycerols by UHPLC–HRMS}},
author = {Jun-Yi Zhou and Yan Zhang and Lu-Lu Wen and Yun Du and Wan-Cheng Zheng and Xiao-Xuan Duan and Miao Qu and Hai-Yu Zhao and Jian-Bo Wan},
journal = {Analytical Chemistry},
year = {2026},
month = oct,
doi = {10.1021/acs.analchem.6c05265},
url = {https://doi.org/10.1021/acs.analchem.6c05265},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chemical Stabilization and Retention-Predictive Modeling for Regiospecific Profiling of Labile Monoacylglycerols by UHPLC–HRMS
AU - Jun-Yi Zhou
AU - Yan Zhang
AU - Lu-Lu Wen
AU - Yun Du
AU - Wan-Cheng Zheng
AU - Xiao-Xuan Duan
AU - Miao Qu
AU - Hai-Yu Zhao
AU - Jian-Bo Wan
PY - 2026
DA - 2026/10/10
JO - Analytical Chemistry
DO - 10.1021/acs.analchem.6c05265
UR - https://doi.org/10.1021/acs.analchem.6c05265
AB - Regiospecific analysis of monoacylglycerols (MAGs) remains challenging because of their low endogenous abundance, the limited availability of regioisomeric standards, and rapid acyl migration between the sn-1 and sn-2 positions during sample handling. Here, we report an UHPLC–HRMS platform integrating chemical stabilization with retention-time prediction for confident profiling of MAG regioisomers in biological samples. Derivatization with 4-pyridineboronic acid (4-PyBA) selectively forms cyclic boronate esters with the glycerol cis-diol moiety, thereby suppressing acyl migration, enhancing electrospray ionization efficiency, and generating characteristic diagnostic ions. To minimize reliance on authentic standards, a three-dimensional quantitative structure–retention relationship (3D-QSRR) model was developed to predict chromatographic retention across structurally diverse MAGs. In parallel, a homologous series of fatty acid 1,2-pentanediol monoesters was synthesized as retention calibrants to correct retention time (RT) drift and improve method robustness. These components were integrated into a targeted parallel reaction monitoring (PRM) workflow supported by an in-house database of 288 annotated sn-1 and sn-2 MAGs. Application of this strategy to serum, brain, colon, and fecal samples from APP/PS1 mice and to serum samples from individuals with Alzheimer’s disease (AD) enabled the confident annotation of 118 endogenous MAGs, including 68 MAGs not currently catalogued in major public databases. Collectively, this integrated platform improves structural confidence and analytical robustness and establishes a transferable framework for regioisomer-resolved analysis of labile glycerolipids.
SN - 0003-2700
SN - 1520-6882
ER -