[Study on metabolites in vivo of Dangefentong Capsules based on UHPLC-Q/Orbitrap-MS/MS]

Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(18):5052-5063. doi: 10.19540/j.cnki.cjcmm.20220421.703.
[Article in Chinese]

Abstract

Dangefentong Capsules is a new traditional Chinese medicine preparation for the treatment of diabetic peripheral neuropathy. It is based on the Salviae Miltiorrhizae Radix et Rhizoma-Puerariae Lobatae Radix herb pair with salvianolic acids, tanshinones and pueraria flavonoids as main components. Studying the chemical composition in vivo of Dangefentong Capsules and its metabolites is of great significance for making clear its pharmacodynamic material basis and the action mechanism. The UHPLC-Q/Orbitrap-MS/MS was applied to rapidly analyze the metabolites and metabolic pathways of Dangefentong Capsules in Beagle dogs after gavage. Eclipse plus C_(18) column(2.1 mm×50 mm, 1.8 μm) was used, and gradient elution was performed with 0.1% formic acid aqueous solution(A)-formic acid acetonitrile solution(B). A heated electrospray ion source(HESI) was employed. The scanning mode was set as the positive and negative ion mode, and the mass scanning range was m/z 100-1 000. The plasma, urine and feces samples were collected after male Beagle dogs were administered with Dangefentong Capsules. The prototype components and metabolites were identified by UHPLC-Q/Orbitrap-MS/MS analysis combined with reference substances and references. The results showed that 107 chemical components were identified, including 58 prototype components and 49 metabolites. The identified prototype components included 42 components from Salviae Miltiorrhizae Radix et Rhizoma and 16 components from Puerariae Lobatae Radix. The metabolites consist of 21 and 28 metabolites of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix, respectively. They are mainly derived from the methylation, hydroxylation, sulfation and glucuronidation of salvianolic acids, tanshinones and pueraria flavonoids. This research rapi-dly analyzes the chemical components in vivo of Beagle dogs administered with Dangefentong Capsules, laying a basis for illustrating the pharmacodynamic material basis and mechanism of Dangefentong Capsules.

Keywords: Dangefentong Capsules; UHPLC-Q/Orbitrap-MS/MS; metabolites; prototype components.

MeSH terms

  • Abietanes
  • Acetonitriles
  • Alkenes
  • Animals
  • Capsules
  • Chromatography, High Pressure Liquid / methods
  • Dogs
  • Drugs, Chinese Herbal* / chemistry
  • Flavonoids
  • Formates
  • Male
  • Polyphenols
  • Pueraria*
  • Tandem Mass Spectrometry

Substances

  • Abietanes
  • Acetonitriles
  • Alkenes
  • Capsules
  • Drugs, Chinese Herbal
  • Flavonoids
  • Formates
  • Polyphenols
  • salvianolic acid
  • tanshinone