UPLC-MS/MS method for the determination of the herb composition of Tangshen formula and the in vivo pharmacokinetics of its metabolites in rat plasma

Phytochem Anal. 2022 Apr;33(3):402-426. doi: 10.1002/pca.3098. Epub 2021 Dec 14.

Abstract

Introduction: Tangshen formula (TSF) is a traditional Chinese medicine composed of seven medicinal herbs including Astragalus membranaceus, Rehmannia glutinosa Libosch, Citrus aurantium L., etc. which is used to treat diabetic nephropathy III, IV qi and yin deficiency and stasis syndrome. Most of the studies on TSF are pharmacological and pharmacodynamic experiments. There are few basic studies on its chemical substances, and the effective constituents are not clear.

Objective: To analyse the main chemical components of TSF and the absorbed components in rat plasma following oral administration based on liquid chromatography tandem mass spectrometry (LC-MS/MS). Moreover, providing a rapid and valid analytical strategy for simultaneous determination of six components in rat plasma and use it in pharmacokinetic studies.

Results: A total of 132 components were identified in TSF, and 44 components were identified in rat plasma after oral TSF, 35 of which were prototype components and nine were metabolic components. A sensitive and reliable LC-MS/MS method was developed for simultaneous determination of six components in rat plasma. The intra-day and inter-day precision relative standard deviation (RSD) was lower than 15%; the accuracy of low, medium and high concentrations ranged from 80% to 120%. The recovery met the requirements and the RSD of the recoveries was less than 15%.

Conclusion: A total of 132 components were identified in TSF. The LC-MS/MS quantitative method for the simultaneous determination of morroniside, loganin, notoginsenoside R1 , ginsenoside Re, ginsenoside Rb1 and astragaloside IV in rat plasma was established for the first time. The pharmacokinetic parameters are clarified, which can guide the clinical medication of TSF.

Keywords: LC-MS/MS; Thermo Q Exactive™ Plus Orbitrap™ mass spectrometer; chemical constituents; pharmacokinetics; traditional Chinese medicines.

MeSH terms

  • Administration, Oral
  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / methods
  • Drugs, Chinese Herbal* / chemistry
  • Rats
  • Tandem Mass Spectrometry* / methods

Substances

  • Drugs, Chinese Herbal
  • tangshen