Midazolam and haloperidol for palliative sedation: physicochemical stability and compatibility of parenteral admixtures

  • Gabriel Estan-Cerezo Servicio de Farmacia-Hospital General Universitario de Elche-FISABIO
  • Francisco José Rodríguez-Lucena Servicio de Farmacia-Hospital General Universitario de Elche-FISABIO
  • Carmen Matoses Chirivella Servicio de Farmacia-Hospital General Universitario de Elche-FISABIO
  • Inmaculada Jiménez-Pulido Servicio de Farmacia-Hospital General Universitario de Elche-FISABIO
  • Ana García-Monsalve Servicio de Farmacia-Hospital General Universitario de Elche-FISABIO
  • Andrés Navarro-Ruiz Servicio de Farmacia-Hospital General Universitario de Elche-FISABIO
Keywords: Midazolam/pharmacology, Haloperidol/pharmacology, HPLC/methods, Additives in Sanitizing Products, Chemical stability, Physical stability, Physicochemical properties

Abstract

This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.

Downloads

Download data is not yet available.
Published
2019-11-29
How to Cite
Estan-Cerezo, G., Rodríguez-Lucena, F. J., Chirivella, C., Jiménez-Pulido, I., García-Monsalve, A., & Navarro-Ruiz, A. (2019). Midazolam and haloperidol for palliative sedation: physicochemical stability and compatibility of parenteral admixtures. Brazilian Journal of Pharmaceutical Sciences, 55, e17351. https://doi.org/10.1590/s2175-97902019000117351
Section
Articles