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

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.