title: Nontargeted diagnostic ion network analysis (NINA): A software to streamline the analytical workflow for untargeted characterization of natural medicines.
abstract: The characterization of herbal prescriptions serves as a foundation for quality control and regulation of herbal medicines. Previously, the characterization of herbal chemicals from natural medicines often relied on the analysis of signature fragment ions from the acquired tandem mass spectrometry (MS/MS) spectra with prior knowledge of the herbal species present in the herbal prescriptions of interest. Nevertheless, such an approach is often limited to target components, and it risks missing the critical components that we have no prior knowledge of. We previously reported a "diagnostic ion-guided network bridging" strategy. It is a generally applicable and robust approach to analyze unknown substances from complex mixtures in an untargeted manner. In this study, we have developed a standalone software named "Nontargeted Diagnostic Ion Network Analysis (NINA)" with a graphical user interface based on a strategy for post-acquisition data analysis. NINA allows one to rapidly determine the nontargeted diagnostic ions (NIs) by summarizing all of the fragment ions shared by the precursors from the acquired MS/MS spectra. A NI-guided network using bridging components that possess two or more NIs can then be established via NINA. With such a network, we could sequentially identify the structures of all the NIs once a single compound has been identified de novo. The structures of NIs can then be used as "priori" knowledge to narrow the candidates containing the sub-structure of the corresponding NI from the database hits. Subsequently, we applied the NINA software to the characterization of a model herbal prescription, Re-Du-Ning injection, and rapidly identified 56 herbal chemicals from the prescription using an ultra-performance liquid chromatography quadrupole time-of-flight system in the negative mode with no knowledge of the herbal species or herbal chemicals in the mixture. Therefore, we believe the applications of NINA will greatly facilitate the characterization of complex mixtures, such as natural medicines, especially when no advance information is available. In addition to herbal medicines, the NINA-based workflow will also benefit many other fields, such as environmental analysis, nutritional science, and forensic analysis.
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Hui
authors: H
authors: Ye
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Lin
authors: L
authors: Zhu
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Di
authors: D
authors: Sun
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Xiaozhuo
authors: X
authors: Luo
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Gaoyuan
authors: G
authors: Lu
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Hong
authors: H
authors: Wang
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Jing
authors: J
authors: Wang
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Guoxiu
authors: G
authors: Cao
authors: Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang, China.
authors: Wei
authors: W
authors: Xiao
authors: Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang, China.
authors: Zhenzhong
authors: Z
authors: Wang
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China.
authors: Guangji
authors: G
authors: Wang
authors: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 21009, China. Electronic address: hhp_770505@hotmail.com.
authors: Haiping
authors: H
authors: Hao
mesh_terms: D001688:Biological Products / Q000032:analysis*; D004365:Drugs, Chinese Herbal / Q000032:analysis*; D012984:Software / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D001688:Biological Products; D004365:Drugs, Chinese Herbal
keywords: Global characterization; LC–MS/MS; Natural medicines; Nontargeted diagnostic ion network analysis (NINA); Nontargeted diagnostic ions (NIs)