Stability Study and Identification of Degradation Products of Caffeoylgluconic Acid Derivatives from Fructus Euodiae.

Huijuan Yu,Yuefei Wang,Jiamin Ding,Zhenzuo Jiang,Xin Chai,Jing Yang,Ying He

doi:10.3390/molecules23081975

Abstract

Caffeoylgluconic acid derivatives are characteristic constituents isolated from the aqueous extract of Fructus Euodiae. In this research focusing on caffeoylgluconic acid derivatives, trans-caffeoyl-6-O-d-gluconic acid (CGA), trans-caffeoyl-6-O-d-gluconic acid methyl ester (CGA-ME), and trans-caffeoyl-6-O-d-glucono-γ-lactone (CGA-LT), a systematic study of stability was performed under different temperatures and pH levels by ultra performance liquid chromatography-diode array detector (UPLC-DAD) and ultra performance liquid chromatography-diode array detector/electrospray ionization-quadrupole-time of flight mass spectrometry (UPLC-DAD/ESI-Q-TOF MS). From the concentration–time curves and sensitivity index (SeI), it was found that compared to CGA, which is inert to the variation of temperature and pH in the tested range, CGA-ME and CGA-LT were more sensitive, with stabilities more likely to be influenced by temperature. Considering the stability index (StI), the integrated stability of CGA was the best, and that of CGA-ME was the worst. In terms of the quasi-molecular and fragment ions of the tested compounds, the degradation products were identified or tentatively characterized, which could shed light on the degradation pathways. CGA-ME and CGA-LT were easily converted to CGA by hydrolytic reaction, all of which were susceptible to the formation of isomers. This study elucidated the degradation mechanism of caffeoylgluconic acid derivatives, contributing to better guidance on manufacturing and controlling the quality of drugs.

Highlights

Traditional Chinese medicines (TCMs) are in widespread use around the world as complementary therapy, increasingly concerned in Western nations [1,2]
It is well known that TCMs and their preparations generally exert their therapeutic effects through the synergic effects of multiple active ingredients [5,10,11]
caffeoyl-6O-D-gluconic acid (CGA), caffeoyl-6-O-D-gluconic acid methyl ester (CGA-ME), and CGA-LT, were the representative compounds existing in Fructus Euodiae (FE)

Summary

Introduction

Traditional Chinese medicines (TCMs) are in widespread use around the world as complementary therapy, increasingly concerned in Western nations [1,2]. The stability of active compounds from TCMs has attracted especially extensive attention, having a vital influence on their quality, safety, and efficacy (QSE) [3,4,5,6,7]. Drug regulatory agencies around the world have drafted guidelines for manufacturing and controlling the QSE of drugs. Drug stability and degradation studies are an integral part of drug development. Stability testing is an important approach to evaluate the quality of drug substances and products, which may vary with time under the influence of temperature, humidity, light, etc. In order to comply with the stringent requirements of regulatory guidelines, quality control and stability studies have taken a front seat in the TCM development process. It is much more complicated to guarantee QSE under the influence of Molecules 2018, 23, 1975; doi:10.3390/molecules23081975 www.mdpi.com/journal/molecules

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