Prediction of incompatibility of ceftriaxone sodium with calcium ions using the ionic product

The purpose of this study was to evaluate the incompatibility of ceftriaxone sodium with calcium-containing products using the ionic product of precipitation, and the measurement of insoluble microparticles using a light obscuration particle counter. Appropriate volumes of 2% (w/v) calcium chloride solution were added to 0.4-2 mg/ml ceftriaxone isotonic sodium chloride solution, to make solutions with a final calcium ion concentration of 1.25 mmol/l. The solutions were gently agitated and stored at 37 degrees C for 24 h. The number of insoluble microparticles with a diameter less than 10 microm in the mixed sample solution, determined using a light obscuration particle counter, was increased when the ceftriaxone concentration was > or =0.8 mg/ml. The Saturation Index (defined as the ratio of the ionic product to the solubility product constant) of the prepared mixed solution was 1.1. A white precipitate could be observed visually when the ceftriaxone concentration of the sample solution was 7 mg/ml; the Saturation Index of the solution was 9.7. The effect of the calcium source on incompatibility with ceftriaxone sodium was also evaluated. The numbers of insoluble microparticles in sample solutions made by adding calcium chloride to the sample were significantly higher than those made by adding calcium gluconate. These results suggest that ceftriaxone should not be co-administered with calcium-containing products even if no precipitation is observed visually. There will still be insoluble microparticles caused by incompatibility in the sample solution when the Saturation Index of the solution is over 1.0.