Physical compatibility and chemical stability of atracurium besylate and midazolam hydrochloride during intravenous coinfusion.

Abstract The objective of this study was to evaluate the physical stability and chemical compatibility of midazolam hydrochloride and atracurium besylate for intravenous coadministration at concentrations normally encountered in clinical practice. Commercially available midazolam hydrochloride injection (Versed) and atracurium besylate injection (Tracrium, Glaxo Wellcome) were used to prepare four different drug combinations in 5% dextrose injection. The final concentration of midazolam (as the hydrochloride salt) and of atracurium (as the besylate salt) was 0.1 or 0.5 mg/mL and or 5 mg/mL, respectively. The chemical stability of midazolam and atracurium in combination was evaluated using a stability-indicating high-performance liquid chromatography assay, capable of simultaneous analysis of both compounds, developed in our laboratory Midazolam was detected using an ultraviolet detector and atracurium with a fluorescence detector. The analysis was done at room temperature under fluorescent lighting. All solutions were evaluated for physical stability by inspecting visually under normal fluorescent laboratory lighting for precipitate (against a black background) or gas formation and color change immediately following the admixture and then at one, two and three hours. The pH of these solutions was also measured at each time interval. Under the study conditions all test solutions retained greater than 90% of the initial concentration after three hours. There was no visible evidence of precipitation, color change, or gas formation in the test solution at any time following admixture; and the pH of the solutions was also unchanged during the three-hour study period. Midazolam hydrochloride and atracurium besylate are physicallly stable and chemically compatible for up to three hours at room temperature under normal fluorescent lighting at the concentrations used in this study and may be coinfused at a y-site without loss ofpotecncy.