Citation: Shuai Guo, Kening Li, Bin Li. Parallel on-tissue chemical derivatization for enhanced molecular annotation of spatial carbonyl submetabolome[J]. Chinese Chemical Letters, ;2025, 36(6): 110366. doi: 10.1016/j.cclet.2024.110366 shu

Parallel on-tissue chemical derivatization for enhanced molecular annotation of spatial carbonyl submetabolome

Shuai Guo ^{a, b, 1} ,
Kening Li ^{a, c, 1} ,
Bin Li ^{a, c, *,}

a.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
b.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
c.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China

binli@cpu.edu.cn

Received Date: 9 April 2024
Revised Date: 23 July 2024
Accepted Date: 23 August 2024
Available Online: 7 September 2024

Figures(5)

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is an attractive technology for the visualization of metabolite distributions in tissues. However, detection and identification of low-abundance or poorly ionized metabolites remains challenging. Although on-tissue chemical derivatization (OTCD) holds great promise for improving MALDI MS detection sensitivity and selectivity by modification of specific chemical groups, the available methods for subsequent metabolite annotation are limited. Herein, a laser-assisted chemical transfer (LACT)-based parallel OTCD strategy was established for visualizing and annotating carbonyl metabolites in murine brain tissues. Girard's T and Girard's P reagents were applied for parallel OTCD to generate the characteristic m/z pairs with a 19.969 Da mass shift (±0.020 Da tolerance) for rapid recognition of derivatized metabolites. The similarity of spatial distribution patterns of each m/z pair was further statistically evaluated to remove the ambiguous annotations due to the occurrence of interference compounds. As a result, 90 ion pairs were annotated as candidate carbonyl metabolites, 66 were previously known and 24 were potential unreported carbonyls. Furthermore, the spatial alterations of carbonyl metabolites in the ischemic rat brain were successfully visualized and characterized, including small molecule aldehydes and ketones, long-chain fatty aldehydes, and monosaccharides. This further emphasizes great potential of parallel OTCD strategy for efficient and confident molecular annotation of spatial submetabolomics data associated with brain diseases.
- Mass spectrometry imaging,
- On-tissue chemical derivatization,
- Parallel derivatization,
- Carbonyl metabolites,
- Mass-shift filtering,
- Spatial distribution similarity
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