Systematic investigation for the stability of traditional Chinese medicine injection composition using Shenmai injection as a model

Abstract

Adverse reactions that occur following the injection of traditional Chinese medicines may limit clinical use. A systematic investigation of methods to ensure the safety and stability of traditional Chinese medicine injection was performed using Shenmai Injection as an example. High-performance liquid chromatography with diode-array detection, high-performance liquid chromatography with evaporative light scattering detector, and chemical kinetics were used to study the degradation of the active ingredients (ginsenosides), pharmaceutical excipient (polysorbate 80), and carbohydrates (sucrose, glucose, and fructose) under a variety of pressure conditions (pH, temperature, light, oxidation, and starting concentrations). The main factors affecting the degradation of the ingredients in Shenmai Injection were determined by comparing the differences in the degradation rules of the ingredients in the aqueous solution and Shenmai Injection. Changes in pH of Shenmai Injection were monitored to preliminarily explore the main material factors that lead to its acidification. The results showed that with a pH of <4, the degradation of ginsenosides was accelerated with the enhancement of acidity. In acidic or neutral conditions, the degradation rate of ginsenosides increased with temperature. Alkaline environment, light, and different initial concentrations had no significant effect on the degradation of ginsenosides. For pharmaceutical excipient, increased alkalinity accelerated the degradation of polysorbate 80, which was promoted at high temperatures. The content of polysorbate 80 was almost unchanged in neutral, acidic, and light conditions. The excipient polysorbate 80 had no significant effect on the stability of ginsenosides under acidic or high-temperature conditions. Monosaccharides like glucose and fructose underwent epimerization under certain conditions, and sucrose was hydrolyzed to monosaccharides. Polysorbate 80 and carbohydrates could decrease the pH of the solution under high-temperature conditions, and the acidification of Shenmai Injection was accelerated as the temperature increased. In conclusion, we established a multi-ingredient, multi-factor stability research method. The main factors affecting the degradation of ingredients were clarified, and the stability-related factors causing acidification of Shenmai Injection were preliminarily explored.