Integration of offline two-dimensional chromatography and mass defect filtering-based precursor ion list data acquisition for targeted characterization of diterpenoid alkaloids in the lateral roots of Aconitum carmichaelii

Yang Yu; Changliang Yao; Wenlong Wei; Haojv Li; Yong Huang; Shuai Yao; Hua Qu; Qinhua Chen; Quanxi Mei; Wanying Wu; De-An Guo

doi:10.1016/j.chroma.2022.463554

Integration of offline two-dimensional chromatography and mass defect filtering-based precursor ion list data acquisition for targeted characterization of diterpenoid alkaloids in the lateral roots of Aconitum carmichaelii

J Chromatogr A. 2022 Nov 22:1684:463554. doi: 10.1016/j.chroma.2022.463554. Epub 2022 Oct 6.

Authors

Yang Yu¹, Changliang Yao², Wenlong Wei³, Haojv Li³, Yong Huang³, Shuai Yao³, Hua Qu², Qinhua Chen⁴, Quanxi Mei⁴, Wanying Wu², De-An Guo⁵

Affiliations

¹ Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen 518101, China.
³ Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen 518101, China.
⁵ Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen 518101, China. Electronic address: daguo@simm.ac.cn.

PMID: 36244236
DOI: 10.1016/j.chroma.2022.463554

Abstract

The hyphenated technique of offline two-dimensional (2D) chromatography with high resolution mass spectrometry (MS) was an efficient tool for separation and characterization of components in complex systems such as herbal medicines, especially those co-eluting components or isomers. In this study, we constructed the ultra-performance convergence chromatography (UPC²) × reversed phase (RP) chromatographic separation system and developed a mass defect filtering (MDF)-based precursor ion list (PIL) acquisition method to improve the selectivity and sensitivity of this technique, and the systematic characterization of diterpenoid alkaloids in the lateral roots of Aconitum carmichaelii (namely "Fuzi" in Chinese) was used as an example. The constructed offline 2D separation system showed a good orthogonality of 0.77. Besides, the in-house databases for known and predicted C₁₉- and C₂₀-diterpenoid alkaloids were established by molecular design in Compound Discoverer software for MS data matching and filtering, and two MDF windows were further constructed to screen out more potential diterpenoid alkaloids with novel structures and to obtain the PIL (mass range: even values between 298 and 1020 Da, parent mass width: ±100 mDa) for data acquisition by calculating the m/z values of potential ions using mass range and corresponding mass defect in the MDF windows. In addition, an integrative structure interpretation strategy was developed by integrating elemental composition analysis, ring double bond analysis, neutral loss filtering, diagnostic ion filtering and database matching, etc. As a result, a total of 659 components in the lateral roots of A. carmichaelii were exposed and characterized, including 526 potential new compounds. This strategy showed significant advantages in improving the coverage and selectivity of screening, and could also be applied in systematic characterization of components in other herbal medicines.

Keywords: Aconitum carmichaelii; Diterpenoid alkaloids; Mass defect filtering; Offline two-dimensional chromatography; Precursor ion list.

MeSH terms

Aconitum* / chemistry
Alkaloids* / analysis
Chromatography, Reverse-Phase
Diterpenes* / analysis
Drugs, Chinese Herbal* / chemistry
Ions / analysis
Plant Roots / chemistry
Plants, Medicinal*

Substances

Alkaloids
Diterpenes
Drugs, Chinese Herbal
Ions