Stability of Cephalosporins in Solution in Terms of the Colour of Solution and Impurities

INTRODUCTION. Cephalosporins are injectable antibiotics, which are mainly free from excipients. Testing for impurities (degradation products) and the colour of solution can help evaluate degradation processes in cephalosporin active substances. Therefore, such testing is important for the quality control of cephalosporins.

AIM. This study aimed to evaluate the stability of cephalosporins in aqueous solutions in terms of impurities and the colour of solution and explore the relationship between these quality parameters.

MATERIALS AND METHODS. This study focused on cephalosporin active substances, including cefazolin, cefuroxime, ceftriaxone, and a combination of ceftriaxone and sulbactam (2:1). The colour intensity of aqueous solutions of these antibiotics was examined by visual comparison with reference standards and by spectrophotometry. The absorbance values of 10% cefazolin solution were measured at 430 nm at fixed intervals for 6 days, and those of 1.2% ceftriaxone and ceftriaxone–sulbactam solutions were determined at the maximum absorption wavelength of 450 nm for 11 days and 16 days, respectively. High-performance liquid chromatography (HPLC) was used to determine the content of related substances in solutions of cefazolin (10% and 0.25%), ceftriaxone (1.2% and 0.03%), and the ceftriaxone–sulbactam combination (1.2%, calculated as ceftriaxone). Ceftriaxone solutions were studied for 16 days, and cefuroxime solutions (10% and 0.1%) were studied for 2 days (48 hours). All the test solutions were stored at room temperature in natural light (away from direct sunlight).

RESULTS. During the test period, all the test solutions gradually acquired an intense yellow colour, and their absorbance and related substance content increased accordingly. Diluted solutions of cefazolin, ceftriaxone, and cefuroxime degraded significantly faster than the solutions of these antibiotics of a higher concentration. The experiment showed that the content of only one or two impurities increased during the first 24–96 hours of degradation, while the content of the remaining related substances changed insignificantly. Cefuroxime proved to be the least stable in aqueous solutions; the content of dezarbomoyl cefuroxime exceeded the limit specified by the regulatory requirements by 2.5 times after 24 hours of storage. The colour of 1.2% ceftriaxone deviated from the regulatory requirements after 24 hours, and the content of individual impurities exceeded the applicable limit for after 72 hours.

CONCLUSIONS. The study has shown that the stability of cephalosporins in aqueous solutions in terms of impurities and the colour of solution depends on the chemical structure of the substance, the concentration of the solution, and the duration of storage in natural light. A correlation has been demonstrated between the absorbance of cefazolin and ceftriaxone solutions and the content of individual impurities.

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