Stability Testing of Intraventricular Irrigations Diluted in Lactated Ringer's Solution

To evaluate the physical and chemical stability of minute concentrations of daptomycin, nicardipine, tobramycin, and vancomycin diluted in lactated ringer's solution (LR) in concentrations safe for administration via IRRAflow intrathecal irrigation.

Commercially available vials of daptomycin, nicardipine, tobramycin and vancomycin were used to compound intraventricular irrigations in LR. The LR irrigations that were tested include daptomycin 2mg/1000mL, nicardipine 2.5mg/1000mL, tobramycin 4mg/1000mL and vancomycin 4mg/1000mL. All irrigations were stored at room temperature and were not protected from light. Samples for each irrigation were tested at various timepoints via Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) testing in conjunction with visual inspection, pH testing, and light absorbance plating to determine if precipitation occurred. Samples were considered chemically stable if they retained 90% of their initial concentration.

All samples were found to be chemically and physically stable within the tested timepoints except for nicardipine. Vancomycin, daptomycin, and tobramycin were found to be chemically and physically stable at 12 hours. Nicardipine had more than 10% degradation at eight hours yet maintained stability at four hours after compounding. By extrapolating the degradation of nicardipine, our results demonstrate that the compound maintained a concentration greater than 90% at six hours.

With the use of UHPLC-MS/MS, pH testing, and calorimetric absorbance measurement, we found that daptomycin, tobramycin and vancomycin were physically and chemically stable in LR out to 12 hours at room temperature. Nicardipine was found to maintain stability out to 6 hours at room temperature.