Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection. At first, the stability of HSYA in solution and in a Xuebijing injection was investigated, then the mechanisms of the increased stability of HSYA in the XBJ injection were investigated to provide useful information on clinical safety. HSYA stability was investigated as a function of pH and temperature in aqueous solution and an XBJ injection, following the guidelines from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Products were identified by UPLC-MS/MS. HSYA reaction followed first-order kinetics under all conditions. The half-life of HSYA in XBJ was almost 40 times longer than in aqueous solution. The activation energies of HSYA reaction in aqueous solution and XBJ were calculated to be 78.53 and 92.90 kJ∙mol⁻¹ by using Arrhenius equation. The results indicated that HSYA was more stable in XBJ than in aqueous solution. Two products were identified and the mechanism was intra-molecular nucleophilic substitution. The excellent stability of HSYA in XBJ injection partly due to the micelles formed in the injection. The study may provide clues for compatibility in TCM prescription and also provide useful information for further preparation technology research of HSYA and assessment of clinical safety of XBJ.

An approach exploiting ultrahigh-performance liquid chromatography (UHPLC) fingerprints and multivariate chemometrics to explore the rationality of processing for Aconiti Lateralis Radix is here proposed. UHPLC fingerprints were established to analyze crude Aconiti Lateralis Radix and two processed products (black slices and white slices). The implemented chemometrics methods, including Ward’s method and principal component analysis (PCA), could lead to better visualized classification of crude and processed products. Inspection of a Ward’s method dendrogram and PCA score plot indicated that all samples belonged to two clusters (crude group and processed group). Subsequently, partial least squares discriminant analysis (PLS-DA) was conducted to obtain the significant chemical markers for discrimination of the crude and processed productions. Additionally, a counter-propagation artificial neural network (CP-ANN) was performed to confirm the chemical markers obtained from PLS-DA. Finally, the chemical markers were identified using ultrahigh-performance liquid chromatography/quadrupole-time-of-flight mass spectrometer (UHPLC-Q-TOF/MS). This strategy has the potential to assess the rationality of processing for Aconiti Lateralis Radix and other Chinese herbal medicines.

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. Graphical Abstract