Crystallization-induced dynamic resolution R-epimer from 25-OCH3-PPD epimeric mixture.

Abstract

25-OCH3-PPD is a promising antitumor dammarane sapogenin isolated from the total saponin-hydrolyzed extract of Panax ginseng berry and Panax notoginseng leaves. 20(R)-25-OCH3-PPD was more potent as an anti-cancer agent than 20(S)-25-OCH3-PPD and epimeric mixture of 25-OCH3-PPD. This paper describes the rapid separation process of the R-epimer of 25-OCH3-PPD from its epimeric mixture by crystallization-induced dynamic resolution (CIDR). The optimized CIDR process was based on single factor analysis and nine well-planned orthogonal design experiments (OA9 matrix). A rapid and sensitive reverse phase high-performance liquid chromatographic (HPLC) method with evaporative light-scattering detector (ELSD) was developed and validated for the quantitation of 25-OCH3-PPD epimeric mixture and crystalline product. Separation and quantitation were achieved with a silica column using a mobile phase consisting of methanol and water (87:13, v/v) at a flow rate of 1.0mL/min. The ELSD detection was performed at 50°C and 3L/min. Under conditions involving 3mL of 95% ethanol, 8% HCl, and a hermetically sealed environment for 72h, the maximum production of 25(R)-OCH3-PPD was achieved with a chemical purity of 97% and a total yield of 87% through the CIDR process. The 25(R)-OCH3-PPD was nearly completely separated from the 220mg 25-OCH3-PPD epimeric mixture. Overall, a simple and steady small-batch purification process for the large-scale production of 25(R)-OCH3-PPD from 25-OCH3-PPD epimeric mixture was developed.

• Authors: Sainan Zhang, Yun Tang, Jiaqing Cao, Chen Zhao, Yuqing Zhao
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 1005 Pg. 39-46 (Nov 15 2015) ISSN: 1873-376X [Electronic] Netherlands
• PMID: 26491820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• 25-methoxydammarane-3,12,20-triol
• Antineoplastic Agents
• Triterpenes

Topics

• Analysis of Variance
• Antineoplastic Agents (analysis, chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid (methods)
• Crystallization (methods)
• Drug Stability
• Humans
• Isomerism
• Light
• Linear Models
• Reproducibility of Results
• Scattering, Radiation
• Sensitivity and Specificity
• Triterpenes (analysis, chemistry, isolation & purification, pharmacology)