Photodestabilization of epinephrine by sodium metabisulfite.
The effect of light and bisulfite on infusion solutions containing epinephrine (2 micrograms/mL), bupivacaine hydrochloride (1 mg/mL), fentanyl (2 micrograms/mL) and sodium edetate (0.18 microgram/mL) was investigated. Solutions were made isotonic using sodium chloride, and they contained either 1.82 micrograms/mL sodium metabisulfite or no metabisulfite at all. The infusions were stored in polypropylene infusion bags (550 mL) and were subjected to light from a xenon burner with a specter similar to sunlight behind a glass window. The contents of epinephrine, bupivacaine and fentanyl were determined with stability indicating methods using a HPLC system. In two identical experiments epinephrine was demonstrated to be more stable under irradiation in the absence of sodium metabisulfite (89.3% and 91.3% remaining of initial concentration) than in its presence (64.5% and 60.1% remaining). Bupivacaine and fentanyl showed no degradation as a function of light exposure, and the stability was not affected by the presence or absence of bisulfite. After two weeks exposure to natural light (Oslo, 60 degrees N, March) the content of epinephrine was 45.0% of the initial concentration in the solutions containing bisulfite and 95.6% in the solutions without bisulfite (n = 3). The relationship between various concentrations of bisulfite and the photo-stability of three epinephrine solutions (2 micrograms/mL, 20 micrograms/mL and 110 micrograms/mL) were tested. The results indicated that approximately equimolar concentration of epinephrine compared to bisulfite, or bisulfite in some excess, was least favorable to the stability of epinephrine. A possible explanation for the photo-destabilizing effect of bisulfite can be the conversion of superoxide radicals (O2-) to highly reactive hydroxyl radicals (.OH) by bisulfite. From these results it can be concluded that solutions containing epinephrine and bisulfite should be protected from light not only during storage but also during use in cases where the infusion time amounts to several days. An alternative, wherever possible, would be to omit bisulfite in the solutions.
Brustugun
J
J
National Hospital Pharmacy, Oslo, Norway.
Tønnesen
H H
HH
Klem
W
W
Kjønniksen
I
I
D015360:Analgesia, Epidural; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D000975:Antioxidants / Q000494:pharmacology*; D002045:Bupivacaine; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D004837:Epinephrine / Q000032:analysis / Q000737:chemistry*; D005283:Fentanyl; D006863:Hydrogen-Ion Concentration; D008027:Light; D010592:Pharmaceutic Aids / Q000494:pharmacology*; D015203:Reproducibility of Results; D013447:Sulfites / Q000494:pharmacology*; D013678:Technology, Pharmaceutical / Q000379:methods*
D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D000975:Antioxidants; D010592:Pharmaceutic Aids; D013447:Sulfites; C005200:sodium metabisulfite; D005283:Fentanyl; D002045:Bupivacaine; D004837:Epinephrine