Study on the Formation Mechanisms of the Degradation Products of Salvianolic Acid A

Background: Salvianolic acid A (Sal A) is one of the major water-soluble compounds isolated from the root of Salvia miltiorrhiza, which is widely used as a kind of traditional Chinese medicine. Because of instability of Sal A, the degradation products of Sal A were studied to confirm the conversion of Sal A. Methods: To elucidate the structures of the degradation products, they were isolated by preparative high performance liquid chromatography (HPLC) and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS). To understand the formation pathways of the degradation products, stress testing and esterification of Sal A were performed and analyzed on HPLC. Results: Five products were identified as a pair of epimers (products 1 and 2), isosalvianolic acid C (3), salvianolic acid C (4) and salvianolic acid A methyl ester (5). Sal A in high humidity yielded 1 and 2 by electrophilic addition. Sal A in strong basic solution yielded 3 by a free radical intermediate. Sal A in high temperature or base or oxidant in water yielded 4 by an epoxide intermediate. Sal A in methanol yielded 5 by esterification catalyzed by acid. Eight other products were found in heated water solution. Conclusion: According to the formation mechanisms of the products, Sal A could be used in a solid form formulation and should be protected from humidity, oxidant and base when manufacturing, depositing and supplying.