Determination of 25-OCH3-PPD and the related substances by UPLC-MS/MS and their cytotoxic activity

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jun 1:1022:274-280. doi: 10.1016/j.jchromb.2016.04.031. Epub 2016 Apr 19.

Abstract

20(R)-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH3-PPD) is a promising antitumor compound belonging to triterpenoid saponins isolated from radix notoginseng. A systematic research on the related impurities in raw material of 25-OCH3-PPD has not been conducted. In this study, three impurities obtained by HPLC-ELSD and characterized by (13)C NMR and MS were observed in the raw material of 25-OCH3-PPD. Cytotoxic activities of the related substances were also evaluated, of which impurity B with 25-OCH3-PPD showed synergistic inhibitory activity against BGC-823 with IC50 values of 8.33μM. Furthermore, a rapid and selective UPLC-MS/MS method was developed for simultaneous determination of the principal component and three related substances in the raw material of 25-OCH3-PPD. Multiple reaction monitoring scan mode was used for the quantification of 20(R)-25-OCH3-PPD and its three related substances. The four constituents were separated within 11min on a BEH C18 column (100 mm×2.1mm, 1.7μm) using a mobile phase comprising methanol and 0.03% formic acid water (82:18, v/v) at a flow rate of 0.2mL/min. The proposed UPLC-MS/MS method displayed acceptable levels of linearity, precision, repeatability, and accuracy. In addition, the proposed method was successfully applied for the establishment of a rational quality control standard for the raw material of 25-OCH3-PPD.

Keywords: 25-OCH(3)-PPD; Related impurities; Synergistic anticancer effects; UPLC–MS/MS.

MeSH terms

  • Antineoplastic Agents / analysis*
  • Cell Line, Tumor
  • Cell Survival
  • Chromatography, High Pressure Liquid / methods*
  • Ginsenosides / analysis*
  • Humans
  • Linear Models
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*

Substances

  • 20(R)-25-methoxyldammarane-3beta,12beta,20-triol
  • Antineoplastic Agents
  • Ginsenosides