Table 1.
Applications of LC−MS in TCM qualitative analysis.
| TCM sample | Mass analyzer | Data acquisition technique | Data post-processing technique | Characterization result | Ref. |
|---|---|---|---|---|---|
| Acanthopanax senticosus | Q-TOF | MSAll; SWATH | DIF | 89 triterpene saponins, along with 14 sapogenins, including 33 potentially new compounds and the first report of malonyl-saponin in genus Acanthopanax | 22 |
| Poria cocos | Q-TOF | IMS-MSE | DM; NLF | 121 lanostane-type triterpene acids, including three new compounds | 23 |
| Yi-Xin-Shu capsule | Q-TOF | PIL-MS/MS | DIF | 276 compounds, including 50 lignans, 30 tanshinones, 4 lactones, 18 flavones, 14 phenolicacids, 1 triterpenoid acid, 3 ophiopogonins, 7 astragalus saponins, and 149 ginsenosides | 24 |
| Erzhi pill | Q-Orbitrap | Full MS/PIL/dd-MS2; “If idle-pick others” (IIPO); DE | MDF; NLF; DIF | 146 components, including 25 triterpenes, 31 flavonoids, 46 iridoids, 16 phenylethanols, 3 coumarins, 12 phenols, and 13 others | 25 |
| Uncaria sinensis (stem, leaf, and flower) | LTQ-Orbitrap | PIL-DE-CID/MS2-HCD/MS3 | BS; MDF; DM | 158 potentially new alkaloids, including 10 unknown but predicted and 108 unexpected ones | 26 |
| Three different parts (the root, stem leaf, and flower bud) of Panax quinquefolius L. | Q-Orbitrap | Full MS/PIL/IIPO/dd-MS2; DE | MDF | 347 saponins (147 from root, 173 from stem leaf, and 195 from flower bud), and 157 thereof not ever-isolated from the Panax genus | 27 |
| Puerarin lobate (Gegen) | LTQ-Orbitrap | PIL; DE | NLF | 66 compounds, including 43 malonates of isoflavone glycoside | 28 |
| Panax ginseng, P. quinquefolius, and P. notoginseng | LTQ-Orbitrap | ISCID-FS; PIL-HCD-MS/MS; DE | NLF | 101 malonyl-ginsenosides, including 69 from P. ginseng, 52 from P. quinquefolius, and 44 from P. notoginseng | 29 |
| Eleutherococcus senticosus leaves | LTQ-Orbitrap | HCD-MS2; PIL-CID-MS4; FS-MS | MN; DM | 106 triterpene saponins including 49 potentially new ones | 30 |
| Carthamus tinctorius L. (safflower) | Q-Orbitrap | full MS/PIL/dd-MS2; IIPO; DE | Retention behavior; Reference compounds comparison; Elemental composition analysis; Fragmentation pathways interpretation; DM | 13 primary metabolites (1 nucleoside, 2 sugars, 5 organic alkali/acids, and 5 amino acids) and 135 secondary metabolites (97 quinochalcone C-glycosides and 38 flavonoids) | 31 |
| Ligustri Lucidi Fructus | Q-Orbitrap | Full MS/PIL/dd-MS2; IIPO; DE; Polarity switching | Reference compounds comparison; Elemental composition analysis; Fragmentation pathways analysis; DM | 158 components, including 137 in the negative mode and 21 in the positive mode | 32 |
| Citrus reticulata Blanco (leaves) | LTQ-Orbitrap | FS-PIL-DE | DIF | 135 polymethoxylated flavonoids, including 81 polymethoxyflavones, 54 polymethoxyflavanones or polymethoxychalcones | 33 |
| Salvia miltiorrhiza | LTQ-Orbitrap | PIL-MSn; DE | Predicted compounds filtering; Total ion chromatogram filtering; Fragment ion search | 190 polymeric phenolic acids, including 18 first detected ones | 34 |
| Lonicerae Japonicae Flos | Q-Obitrap | EL-dd-MS2 | DM; MN | A total of 537 compounds, including a large number of potential novel structures | 36 |
| Venenum bufonis | LTQ-Orbitrap | FS-DE-MS1; HCD-MS2 (−); CID-MS2 (−); CID-MS3 (−); Product ion-MS4 (−); CID-MS2 (+); NL-MS3 (+) | – | 78 dicarboxylic acid conjugated bufotoxins, including 68 new compounds, 25 types of substructure formulas and seven dicarboxylic acid side chains | 38 |
| Roots, leaves, and flower buds of Panax ginseng, P. quinquefolius, and P. notoginseng | LTQ-Orbitrap | ISCID-FS-MS1; Mass tag/CID-MS2; NLS/HCD-MS3; DE | – | 178 malonylginsenosides | 41 |
| Panax ginseng, Panax quinquefolius, and Panax notoginseng | LTQ-Orbitrap | ISCID-FS-MS1; Mass tag/CID-MS2; Product ion scan/CID-MS3; DE | NLF | 216 carboxyl-free ginsenosides | 42 |
| Processed Aconitum roots (Shengfuzi, Heishunpian, Baifupian, Zhichuanwu, and Zhicaowu) | QTOF; QqQ | PIS | – | 24 benzoyl-containing alkaloids | 46 |
| Cynara scolymus L. | Q-TRAP | PIS | – | 10 caffeoylquinic acid derivatives | 47 |
| Tussilago farfara L. (buds) | QqQ; QTOF | PIS; Product ion scan | – | 74 oplopane- and bisabolene- sesquiterpenoids, and isolation of 11 compounds | 48 |
| Glycyrrhiza yunnanensis | QqQ; QTOF | NLS; PIS | – | 50 triterpene saponins | 49 |
| Marsdenia tenacissima (Roxb.) Wight et Arn. | QqQ | PIS; FS; Product ion scan | DIF; NLF | 110 polyoxypregnane and its glycosides | 50 |
| Nicotiana tabacum | QqQ | Two-step PIS | – | 17 flavonoids, including 9 newly identified ones | 51 |
| Danhong injection | QTRAP | EMS-IDA-EPI; PIS-IDA-EPI | DM | 90 compounds, including 46 salvianolic acids and related phenolic compounds | 52 |
| Juglans cathayensis | QTRAP; QTOF | EMS-EPI; Stepwise MIM-EPI; PIS-EPI | NLF | 48 naphthoquinones including 24 novel ones | 53 |
| Radix Glehniae | QTRAP | MIM-IDA-EPI; PIS-IDA-EPI | – | 41 coumarins | 54 |
| Cistanche deserticola and C. tubulosa | QTRAP | EMS-IDA-EPI; Predefined MRM-IDA-EPI; PIS-IDA-EPI; NL-IDA-EPI | DM | 513 components detected, including 379 annotated compounds | 55 |
| Tobacco leaves | QqQ | NLS; Product ion scan | DM | 64 glycosides, including 39 glycosides linked with monosaccharides, 18 glycosides linked with disaccharides and 7 glycosides linked with trisaccharides | 56 |
| Astragali Radix (Huangqi) | QTRAP | MIM-EPI; PI-EPI; NL-EPI; MRM-EPI | Extracted ion chromatogram; DIF; NLF | 421 flavonoids | 57 |
| Astragali Radix | QTRAP | NL/PIS-IDA-enhanced resolution-EPI | – | 136 triterpenoid saponins | 58 |
| Flaveria (F. robusta, F. pringlei, F. linearis, F. anomala, F. australasica, and F. bidentis) seeds | QTRAP | NLS | – | 27 sulfated flavonoids | 59 |
| Carthamus tinctorius L. | Ion trap | FS; MSn; MRM | DIF; NLF | 77 flavonoid glycosides | 60 |
| Alismatis Rhizoma and processed Alismatis Rhizoma | QTOF; QTRAP | FS; MS/MS; MRM | DIF; NLF | 80 triterpenes including 14 novel compounds; 7 more triterpenes compounds in the processed Alismatis rhizoma | 61 |
| Isodon serra | QTRAP | MRM-IDA-EPI | – | 27 components, including eighteen diterpenoids, six phenolic acids, and three flavonoids | 62 |
| Turmeric | TripleTOF; QTRAP | CID-MS/MS; MRM-EPI | BS; DIF; Ring double bond equivalents calculation | 96 curcuminoids | 63 |
| Ginseng, American ginseng, and processed products | QTRAP | Step-wise MRM-IDA-EPI; sMRM | PCA | 221 ginsenosides, including 185 annotated ones | 64 |
| Shenfu injection | QTRAP | Predefined MRM-IDA-EPI; Step-wise MIM-IDA-EPI | DM | 157 detected hydrophilic compounds, and 154 of which were identified as amino acids, nucleosides, organic acid, carbohydrates, etc.; 40 primary hydrophilic and hydrophobic ingredients including 11 amino acids, 9 nucleosides, 9 aconite alkaloids, and 11 ginsenosides | 69 |
| Carthamus tinctorius L. | LTQ-Orbitrap | FS-MS1; CID-MS2; CID-MS3; DE-HCD-MS/MS | DIF; Ring double bond equivalent; Characteristic UV absorption; Diagnostic product ions analysis | 163 quinochalcone C-glycosides homologs, including 149 potential new ones | 70 |
| Carthamus tinctorius L. | LTQ-Orbitrap | CID-MS1-MS2-MS3; DE-HCD-MS1-MS2 | DIF; NLF; DM | 107 flavonoids, including 80 newly reported flavonoid O-glycosides | 71 |
| Ophiopogon japonicus | Q-TOF; IT-TOF | FS; MS1-MS2-MS3 | MDF | More than 50 ophiopogonins and 27 ophiopogonones | 77 |
| Yin Chen Si Ni Tang | Q-TOF | MSE | MDF | 62 Aconitum alkaloids | 78 |
| Uncaria rhynchophylla | LTQ-Orbitrap | DE-CID-MS4 | MDF; NLF; DIF; DM | 92 alkaloids (60 free alkaloids and 32 alkaloid O-glycosides), 56 of which were potential new alkaloids for the Uncaria genus | 79 |
| Processed Semen Strychni | IT-TOF | FS; MS2 and MS3 | MDF; DIF | 24 dihydroindole-type alkaloids, including 4 that were previously not described | 80 |
| Citrus reticulata Blanco | LTQ-Orbitrap | MS and MS/MS | MDF; DIF | 81 polymethoxylated flavonoids, including 50 polymethoxyflavones and 31 polymethoxyflavanones or polymethoxychalcones | 81 |
| Folium Artemisiae Argyi | Q-Orbitrap | FS; MS/MS | NRF; MDF; NLF; DIF | 16 methoxylated flavonoids and 55 chlorogenic acids analogues | 82 |
| Panax notoginseng (Sanqi) | Q-TOF | MS; Auto MS/MS; targeted MS/MS | MDF; Characteristic isotopic distribution | 234 ginsenosides including 67 potential new ones | 83 |
| Five botanical origins of Uncariae Ramulus Cum Unicis | LTQ-Orbitrap | DE-step-wise PIL-CID/MS2-HCD/MS3 | Elemental composition analysis; NLF; DIF; DM | 1227 indole alkaloids | 84 |
| Er-xian decoction | LTQ FT | FS; DE-CID-MS2; CID-MS3 | MTSF; Discriminant analysis; BS | 553 potential compounds and 66 candidates | 87 |
| Arnebiae Radix | Q-Orbitrap | Full MS; MS/MS | BS; DM; MDF | 96 compounds, 13 of which were confirmed by the reference standards, 30 with a low abundance, and 9 unknowns | 88 |
| Pueraria lobata (Willd.) Ohwi (Gegen) and Pueraria thomsonii (Fenge) | LTQ-Orbitrap | FS; DDA | IPF | 12 S-derivatives were found, 9 of which were tentatively identified | 92 |
| Forsythia suspensa | Q-TOF | MSE; CID-MS/MS | DIF | 8 potentially new C6–C2 glucoside conjugates | 93 |
| Zicao | Q-TOF | MS; MS/MS | BS; DIF; Characteristic product ion filtering | 58 compounds including 32 novel ones | 94 |
| Akebiae Fructus | Q-TOF | MSE | Adduct ion filtering; DIF; Characteristic ion filtering; NLF | 94 compounds (85 triterpenoid saponins and 9 chlorogenic acids), including 9 types of triterpenoid saponins and 2 types of chlorogenic acid; 50 newly discovered constituents | 95 |
| Spatholobus suberectus | Q-TOF | FS in both positive and negative modes; (−)-MS/MS | DM; DIF | 38 compounds, including 36 flavonoids and 2 non-flavonoid compounds | 96 |
| Scutellaria baicalensis | Q-Orbitrap | FS; MS/MS | DIF | 132 compounds, 59 of which were reported for the first time | 97 |
| Amphimas pterocarpoides | LTQ-Orbitrap | FS; MS/MS | DIF | 21 molecules, 17 of which were found to belong to the targeted chemical groups, including 8 isoflavones, 7 dihydroisoflavones and 2 isoflavone glycosides | 98 |
| Roots and berries of raw and steamed American ginseng (P. quinquefolius L.) | TOF; Q-TOF | FS; CID-MS/MS | DIF | 70 saponins | 99 |
| Fresh and processed ginseng | Q-TOF | FS; CID-MS/MS | DIF; NLF | 12 malonyl ginsenosides | 100 |
| Uncaria rhynchophylla | Q-TOF | MS; MS/MS | DIF | A total of 29 compounds, comprising 18 alkaloids, 6 flavonoids, and 5 quinic acids; 4 novel tetracyclic monoterpenoid oxindole alkaloids (TMOAs) | 101 |
| Lycoris spp. (Amaryllidaceae) | Q-TOF | MS; MS/MS | DIF | 37 lycorine-type alkaloids, including 16 previously undescribed compounds | 102 |
| Calyx of Physalis alkekengi L. var. franchetii (Mast.) Makino | Q-TOF | MS; MS/MS | DIF; NLF | 46 physalins, including 20 novel ones | 103 |
| Glechomae Herba | Q-TOF | MS; MS/MS | DIF; NLF | 120 compounds, including 10 chlorogenic acids, 10 gallic acids, 21 phenylpropionic acids and 77 flavonoids; 65 newly discovered constituents; 4 types of chlorogenic acids, 3 types of galloylglucoses, 3 types of phenylpropionic acid skeletons, and 5 types of flavonoid aglycone skeletons | 104 |
| Raw and processed pieces of Rheum palmatum L. | Q-TOF | (−)-MS; (−)-MS/MS | DM; DIF | 73 characteristic markers | 105 |
| Garcinia oblongifolia | QTOF | MS/MS; ISCID MS/MS; ISCID combined with TAP fragmentation; IM-MSE; IM-MS/MS | DIF | 140 potential polycyclic polyprenylated acylphloroglucinols (PPAPs), including 7 pairs coeluting isobaric PPAPs that were indistinguishable by conventional UHPLC−HRMS alone | 106 |
| Shengmai injection | IT-TOF | MS1, MS2, MS3 | DIF | More than 30 ginsenosides and 20 lignans | 107 |
| Guge Fengtong tablet | Q-TOF | FS | DIF | 47 components, including 18 phenolic acids, 8 saponins, 14 gingerol-related compounds, and 7 diarylhepatonoids | 108 |
| Yindan Xinnaotong soft capsule | Q-TOF; QqQ | FS; MRM | DM; DIF; MDF; NLF | 124 compounds, including 44 flavonoids, 31 phenolic acids, 20 tanshi-nones, 16 saponins, 6 ginkgolides, 5 sulfides, camphor and borneol | 109 |
| Roots of Aconitum carmichaelii Debx. | LTQ-Orbitrap | FS; CID-MS2-MS3 | NLF | 42 diester-diterpenoid alkaloids; 23 potential new compounds, including 16 short chain fatty acyls diester-diterpenoid alkaloids, 4 N-dealkyl diester-diterpenoid alkaloids and several isomers of aconitine, mesaconitine and hypaconitine | 112 |
| Saussurea involucrata | LTQ FT | DE-CID-MS3 | MTSF | 38 compounds, including 19 flavones, 11 phenylpropanoids and 8 sphingolipids; among them, 7 flavonoids, 8 phenylpropanoids and 8 sphingolipids were identified for the first time in Saussurea involucrate | 114 |
| Duhaldea nervosa (Wallich ex Candolle) A. Anderberg | LTQ-Orbitrap | FS; CID-MS2; DE | MTSF | 47 chlorogenic acids, including 19 monoacyl-quinic acids, 22 diacyl-quinic acids, and six triacyl-quinic acids | 115 |
| Flos Lonicerae Japonicae | LTQ-Orbitrap | FS; FS-PIL; MIM | DM; MTSF; DIF | 115 chlorogenic acids attributed to 18 categories, most of which were newly reported | 116 |
| Xiao-Xu-Ming decoction | LTQ FT | FS; DE-CID-MS2; CID-MS3 | MTSF | 68 compounds among 3362 detected compounds, including 14 templated compounds (reference compounds), 50 related compounds fished by MTSF technique, and 4 unrelated compounds identified by manual method | 117 |
| Venenum Bufonis | Q-TOF | Fast DDA | MN | 229 bufadienolides, including two subclasses of compounds (bufogeninsconjugated with carboxylic acid and N-heterocyclic bufogenins) which were found in Venenum Bufonis for the first time | 137 |
| Aconiti Lateralis Radix Praeparata and its processed products | Q-TOF | MSE | MN | 145 diterpenoid alkaloids, including 78 C19 (19 diester-diterpenoid alkaloids, 20 monoester-diterpenoid alkaloids, 7 lipo-diterpenoid alkaloids, 32 amine-diterpenoid alkaloids), 13 C20, and 54 other diterpenoid alkaloids | 138 |
| Danhong injection | Q-Orbitrap | FS | SA | 117 compounds, including 76 phenolic acids, 20 flavonoids, and 21 other compounds | 139 |
| Curcuma longa | QqQ | NL/PIS | SA | 846 terpecurcumins (terpene-conjugated curcuminoids), including a number of potentially novel compounds | 140 |
| Magnolia officinalis | Q-TOF | MS; MS/MS | DIF; NLF; SA | 87 phenylethanoid glycosides, including 14 isomers | 141 |
| Ziziphi Spinosae Semen and Ziziphi Mauritianae Semen | Q-TOF | MSE | DM; DIF; NLF | 60 target components in Ziziphi Spinosae Semen, including 27 flavonoids, 16 saponins, 10 alkaloids, 6 terpenes, and 1 other, and 53 nontarget components with 40 new deduced components; 132 chemical components in Ziziphi Mauritianae Semen, including 7 additional nontarget new components | 149 |
| Peanut stems and leaves | Q-TOF | MSE | DM | 283 chemical compounds, including 207 new compounds | 150 |
| White and red ginsengs | Q-TOF | IM-MSE; IM-MS/MS | DM | 201 ginsenosides, including 10 pairs of co-eluting isobaric ginseng saponins | 151 |
| Stems and leaves of Panax ginseng | LTQ-Orbitrap | DE-CID-MS3; DE-HCD-MS2 | NLF; DIF; DM | 646 ginsenosides, including 427 which have not been isolated from the genus of Panax L. | 152 |
| Five different parts (root, leaf, flower bud, berry, and seed) of Panax ginseng | Q-TOF | MSE | DM | 164 compounds | 153 |
| Panax notoginseng | Q-TOF | Fast DDA | DM; DIF; NLF | 945 ginsenosides, including 662 potentially novel ginsenosides | 154 |
| Baoyuan decoction | Q-TOF; QTRAP | FS-MS1; MSE; Predefined MRM-EPI, MIM-EPI, and PIS-EPI | DM; DIF | 236 compounds, including 139 saponins, 83 flavonoids, 6 procyanidins, 4 lignans, and 4 diterpenes | 155 |
| Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz and Paris vietnamensis (Takht.) H. Li | Q-TOF | MSE | DM | 146 metabolites, including 42 potential new compounds | 156 |
| Panax ginseng, P. quinquefolius, and P. notoginseng | Q-TOF | MSE; HDMSE | DM | 24 potential lipid markers enabling the simultaneous differentiation of three Ginseng species | 157 |
| Cistanche deserticola, C. sinensis, and C. tubulosa | LTQ-Orbitrap | FS-HRMS; MS/MS; DE | DM; Parent mass modification search; DIF; MTSF | 69 phenylethanoid glycosides, including 17 new ones | 158 |
| Aconitum carmichaelii Debx. | Q-TOF | MS; MS/MS | DM | 148 lipo-alkaloids, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties | 161 |
| Gelsemium elegans | Q-TOF | MS/MS | DM | 57 components, including 43 alkaloids, 9 iridoids, 2 steroids, 2 phenolic acids and 1 coumarin | 162 |