Compatible stability study of panax notoginseng saponin injection (xueshuantong®) in combination with 47 different injectables

Panax Notoginseng Saponin (PNS) injection (Xueshuantong®, XST) plays an important role in acute and chronic treatment of cardiovascular disease in China. XST, a freeze-dried powder injection of PNS, contains ginsenosides, Rg1, Rb1, Re, Rd. and notoginsenoside, R1. Study of the stability of herbal medicine injections is limited. The degradation products may contribute to adverse drug reactions (ADRs). The stability kinetics and degradation mechanisms of the five ingredients of PNS in XST injection were systematically explored in aqueous solution. The compatible stability of XST injection in combination with 47 injectables was evaluated using biophysical analysis. A principal components analysis model provided a good clustering result after compatibility. The degradation of the five ingredients in aqueous solution was found to be acid, temperature, oxidation and trivalent ion-dependent. All ingredients were much more stable in XST injection than in aqueous solutions. Nine degradation products were identified by adopting LC-Q-TOF/MS. Standards exceeding the osmotic pressure and/or particle size were found to be the probable causes of the ADR, which were related to drug combination. To minimize the risk of ADRs, drug combinations should be avoided until the complicated chemical matrices of the Chinese medicine injections are more clearly understood. Copyright © 2016 John Wiley & Sons, Ltd.