Ti3C2(OH)x-assisted LDI-TOF-MS for the rapid analysis of natural small molecules

Hui Li; Chunxia Ma; Meng Gao; Yong Li; Lei Xie; Dantong Zhao; Runhao Zhang; Guanhua Zhang; Wenhan Li; Rong Rong; Biao Kong

doi:10.1007/s00216-022-04382-z

Ti₃C₂(OH)_x-assisted LDI-TOF-MS for the rapid analysis of natural small molecules

Anal Bioanal Chem. 2022 Dec;414(29-30):8447-8461. doi: 10.1007/s00216-022-04382-z. Epub 2022 Nov 3.

Authors

Hui Li^{1

2

3}, Chunxia Ma², Meng Gao², Yong Li², Lei Xie^{4

5}, Dantong Zhao⁶, Runhao Zhang⁷, Guanhua Zhang², Wenhan Li², Rong Rong¹, Biao Kong^{8

9}

Affiliations

¹ College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
² Shandong Analysis and Test Center, Advanced Materials Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, China.
³ Department of Pharmacy, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China.
⁴ Department of Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200438, China.
⁵ Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, 322000, China.
⁶ Heze Institute for Food and Drug Control, Heze, Shandong, 274000, China.
⁷ Key Laboratory of Advanced Energy Materials Chemistry (MOE), College of Chemistry, Nankai University, Tianjin, 300071, China.
⁸ Department of Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200438, China. bkong@fudan.edu.cn.
⁹ Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, 322000, China. bkong@fudan.edu.cn.

PMID: 36323886
DOI: 10.1007/s00216-022-04382-z

Abstract

The inhomogeneous distribution of co-crystallized analytes and the traditional organic matrices as well as the intensive background interference in the low molecular weight range hinder the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in the analysis of small-molecular compounds. New two-dimensional material MXene (e.g., Ti₃C₂) exerts better hydrophilicity, homogeneity and repeatability, and higher laser desorption efficiency, as well as less background interference than traditional organic matrices and other nanomaterial matrices such as titanium oxide, graphene, and gold nanostructures. This study was aimed to design Ti₃C₂ matrix with abundant hydroxyls on its surface, enhance the stability of this hydroxyl-rich Ti₃C₂ (Ti₃C₂(OH)_x), and evaluate the analytical performances of Ti₃C₂(OH)_x-assisted laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) for small-molecular natural compounds in complex samples. The developed Ti₃C₂(OH)_x showed the distinct advantages such as minimum background interference, high peak intensity (~10⁵), high salt (0.6 M) and protein (0.5 mg/mL) tolerance, good repeatability (relative standard deviation<20%), and good stability after eight months of storage. Ti₃C₂(OH)_x-assisted LDI-TOF-MS analysis could be used to rapidly identify Artemisia annua (a world-famous traditional Chinese medicine) and quantify the contents of the main chemical ingredients (oxymatrine (OXY) and matrine) of Compound Kushen Injection (CKI). Interestingly, the content of OXY in CKI could be accurately quantified by Ti₃C₂(OH)_x-assisted LDI-TOF-MS, and there was a good linear relationship (R² -0.9929), a low limit of detection (400 pg), and a low limit of quantification (600 pg) of OXY. Taken together, the rapid and accurate analysis of small-molecular natural compounds in complicated samples could be achieved by the Ti₃C₂(OH)_x-assisted LDI-TOF-MS analysis.

Keywords: Laser desorption/ionization mass spectrometry (LDI-MS); Matrix; Quantification; Ti3C2(OH)x; Traditional Chinese medicine.

MeSH terms

Gold
Graphite*
Lasers
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
Titanium*

Substances

Titanium
Gold
Graphite

Grants and funding

2019YFC1604600/National Key R&D Program of China