ABSTRACT
The compatibility of kanamycin with sodium citrate for the formulation of kanamycin sulfate injection was determined, including optimization of the amount of sodium citrate in the injection and the sterilization process. An HPLC coupled with an evaporative light scattering detector (ELSD) was used to measure the amount of sodium citrate and the impurity profiles. A validated post-column derivatization HPLC coupled with a fluorescence detector (FLD) was used to determine the correlation between specific impurities in a domestic factory and sodium citrate, and then the formulation was evaluated by HPLC coupled with mass detector (MS) characterization of degradation products. The results show that the amount of sodium citrate in kanamycin sulfate injection from a domestic factory is about 40 times higher than that of the Meiji formulation. Several specific impurities can be detected in solutions heated under simulated sterilization conditions (121 ℃), which were correlated with the amount of sodium citrate. Impurities were characterized by HPLC-MS/MS, and data showed that the identified impurities were interaction products of kanamycin and sodium citrate. These results indicate that greater attention should be directed at formula optimization in domestic factories, as it is crucial to the safety and efficacy of the preparations. Drug-excipient chemical compatibility should also be evaluated in the development of pharmaceutical dosages forms especially when the active pharmaceutical ingredients have a primary amine group.
ABSTRACT
OBJECTIVE: To establish an HPLC method for rapid screening and simultaneous determination of 10 preservatives in eye drops and assess their antimicrobial effectiveness. METHODS: A Waters XBridge C18 column (4.6 mm × 150 mm, 5 μm) was used, and the mobile phase was 0.1% phosphoric acid-methanol-THF eluted in gradient mode at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 214 nm. The antimicrobial effectiveness of the preservatives was assessed according to Ch. P 2015. RESULTS: The calibration curves were linear in the range of the corresponding test concentrations (r=0.999 3 -1.000 0). The recoveries were between 96.1%-101.8%. One of the eye drops products did not meet the requirement of Ch. P 2015. CONCLUSION: The established method is rapid and inexpensive. And it ensures excellent simplicity, sensitivity, specificity, and reproducibility and can be used for rapid screening and determination of the contents of preservatives in eye drops. The amount of preservatives should be established during the R&D period or determined according to the results of antimicrobial effectiveness test rather than using empirical values.