Analytical and Bioanalytical Chemistry

, Volume 411, Issue 29, pp 7747–7760 | Cite as

Systematic quality evaluation of Peiyuan Tongnao capsule by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry and adjusted parallel reaction monitoring of quality markers

  • Chenxi Wang
  • Keyu Feng
  • Zhifei Fu
  • Wenzhi Yang
  • Ping Wang
  • Tao Wang
  • Xiumei Gao
  • Heshui YuEmail author
  • Lifeng HanEmail author
Research Paper


Peiyuan Tongnao capsule (PTC) is a prescription medicine of traditional Chinese medicine with the effects of “nourishing the kidney,” “replenishing essence,” “extinguishing wind,” and “opening the meridian”. PTC is also widely used in clinic for the treatment of stroke and chronic cerebral circulation insufficiency. However, the quality control studies of PTC are hitherto quite limited. Here, we aim to fully utilize an advanced chromatography–mass spectrometry hyphenation technique to qualitatively and quantitatively evaluate the quality of PTC. Firstly, a two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry (2D-LC/Q-Orbitrap-MS) approach was established for multicomponent characterization. An offline 2D-LC system fitted with an Xbridge Amide column and an HSS T3 column showed an orthogonality of 0.63 and a theoretical peak capacity of 6930. Eleven fractions of PTC, after hydrophilic interaction chromatography (first dimension), were further analyzed by reversed-phase ultrahigh-performance liquid chromatography/Q-Orbitrap-MS (UHPLC/Q-Orbitrap-MS, second dimension) using a rapid negative/positive switching mode. Consequently, 178 compounds were separated, 96 of which were identified or tentatively characterized. Secondly, co-condition fingerprint analysis of seven constituted herbal medicines of PTC was performed to unveil ten active ingredients (citric acid, rehmannioside D, echinacoside, paeoniflorin, verbascoside, liquiritin, 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, cinnamic aldehyde, glycyrrhizic acid, and emodin) as the quality markers of PTC. Thirdly, a UHPLC/PRMad (adjusted parallel reaction monitoring) method was established and validated to quantify the ten marker compounds in 14 batches of PTC. To the best of our knowledge, this is the first study to report comprehensive multicomponent characterization, authentication, and quality evaluation of PTC, which could be used to lay the foundation for quality control, biological efficacy research, and further development.

Graphical abstract


Peiyuan Tongnao capsule Offline 2D-LC/Q-Orbitrap-MS Quality markers Quality control Adjusted parallel reaction monitoring 



This study was supported by National Key R&D Program of China (2018YFC1704500) and Tianjin Committee of Science and Technology, China (18JCYBJC94700). Many thanks for sampling support from Henan Lingrui Pharmaceutical Co., Ltd.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.

Supplementary material

216_2019_2119_MOESM1_ESM.pdf (3.8 mb)
ESM 1 (PDF 3853 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chenxi Wang
    • 1
  • Keyu Feng
    • 1
  • Zhifei Fu
    • 1
  • Wenzhi Yang
    • 1
  • Ping Wang
    • 2
  • Tao Wang
    • 1
  • Xiumei Gao
    • 1
  • Heshui Yu
    • 1
    Email author
  • Lifeng Han
    • 1
    Email author
  1. 1.Tianjin State Key Laboratory of Modern Chinese MedicineTianjinChina
  2. 2.Henan Lingrui Pharmaceutical Co., Ltd.Xinxian CountyChina

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