Incompatibility of Erythromycin Lactobionate and Sulfamethoxazole/Trimethoprim with Linezolid Injection

Abstract

The objective of this study was to evaluate the physical compatibility and chemical stability of linezolid 200 mg/100 mL admixed with erythromycin lactobionate 500 mg and separately with sulfamethoxazole 400 mg/trimethoprim 80 mg for up to 7 days at 4° C and 23° C. The test samples were prepared by adding the required amount of erythromycin lactobionate and sulfamethoxazole/trimethoprim to separate bags of linezolid injection. Evaluations were made at the initial time point and at 1, 3, 5, and 7 days of storage at temperatures of 4° C and 23° C for physical and chemical stability. Physical stability was assessed using visual observation in normal light and a high-intensity monodirectional light beam (Tyndall beam). In addition, turbidity and particle content were measured electronically. Chemical stability was evaluated by using stability-indicating high-performance liquid chromatographic (HPLC) analytical techniques. The linezolid admixtures with erythromycin lactobionate were clear and colorless when viewed in normal fluorescent room light and using a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. HPLC analysis found no loss of linezolid in any sample stored at either temperature throughout the study. However, erythromycin lactobionate underwent rapid and extensive losses. Under refrigeration, erythromycin losses were about 45% in 24 hours; at room temperature, losses of over 80% occurred during the first day. The linezolid admixtures with sulfamethoxazole/trimethoprim resulted in gross precipitation nearly immediately upon preparation of all samples. The precipitate consisted of white needle-like crystals. HPLC analysis found that both sulfamethoxazole and trimethoprim had precipitated. Consequently, no further analysis was performed on these samples.