Chemical Stability Testing of Solutions for Intraventricular Irrigations via IRRA flow Ventricular Drain System

Abstract

Purpose: Advances have been made with delivery of medications via continuous intrathecal irrigating ventricular drains such as IRRAflow (IRRAS). Medications including vancomycin, tobramycin, daptomycin and nicardipine are currently being used as ventricular irrigations via the IRRAflow device. The purpose of this study was to evaluate the chemical stability of minute concentrations of daptomycin, nicardipine, tobramycin, and vancomycin for administration via IRRAflow intrathecal catheters. Methods: Commercially available formulations of daptomycin, nicardipine, tobramycin, and vancomycin were each diluted in separate normal saline (NS) 1000 mL bags to final concentrations of daptomycin 2 mg/1000 mL NS, nicardipine 2.5 mg/1000 mL NS, tobramycin 4 mg/1000 mL NS, and vancomycin 4 mg/1000 mL NS. Samples from each compound were transferred into 2.5 mL glass vials and evaluated in triplicate fashion using ultra-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Each injection was analyzed in comparison to its respective calibration curve and a mean result for each time point was determined. The concentration of the samples was tested at 0, 6 and 12-hours for vancomycin, daptomycin, and tobramycin and 0, 4 and 8-hours for nicardipine. All irrigations were kept at room temperature and were not protected from light. Results: All samples tested were found to be chemically stable at various testing time points. Daptomycin retained a mean of 94.3% of initial concentration at 12 hours while tobramycin retained 93.1% of its initial concentration at 12 hours. Vancomycin samples were found to be 92.9% of initial concentration at 12 hours and nicardipine maintained a mean of 90.6% of initial concentration at 8 hours. Future studies could assess these conditions to potentially further stability data. Conclusion: With use of LC-MS, we demonstrated that dilute concentrations of vancomycin, daptomycin, and tobramycin maintain at least 90% of initial concentration for 12 hours at room temperature, whereas nicardipine remained chemically stable for 8 hours at room temperature.