Abstract

Emerging data suggest that intravenous ascorbic acid (AA) may be beneficial in patients with sepsis. Clinicians require data on stability of diluted AA for safe administration. We evaluated the stability of AA diluted in normal saline (NS) or 5% dextrose in water (D5W) solutions over 14 days at 25 °C and at 4 °C, protected from light, using concentrations of 37 mg/mL and 77 mg/mL (Sandoz) and 40 mg/mL and 92 mg/mL (Mylan). We also assessed stability of a 40 mg/mL solution (Mylan) at 25 °C exposed to light for 75 h. Concentrations were measured using liquid chromatographic separation with ultraviolet light detection on days 0, 0.33, 1, 1.33, 2, 3, 4, 7, 10 and 14. By day 14, solutions at 4 °C retained >97.72% of the initial concentration; at 25 °C, solutions retained >88.02% of the initial concentration, but visual changes were evident after day 2. Multiple linear regression demonstrated that study day and temperature (p < 0.001) but not solution type (p = 0.519), concentration (p = 0.677) or manufacturer (p = 0.808) were associated with the percentage remaining. At 75 h, degradation rates were similar in solutions protected from vs. exposed to light. In conclusion, AA solutions are stable for at least 14 days at 4 °C, with protection from light.

Highlights

  • IntroductionAssessing stability of intravenous ascorbic acid (AA) over time is important for the feasibility of ongoing randomized trials and for other clinical applications, such as cancer care [2]

  • Intravenous ascorbic acid has emerged as a potential treatment for sepsis [1].Assessing stability of intravenous ascorbic acid (AA) over time is important for the feasibility of ongoing randomized trials and for other clinical applications, such as cancer care [2]

  • At 25 ◦ C, an 80.0 mg/mL solution of AA in water was immediately degraded to 13.17% remaining when 10 μL of a 0.5% concentration of sodium hypochlorite was added to 0.5 mL of solution

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Summary

Introduction

Assessing stability of intravenous ascorbic acid (AA) over time is important for the feasibility of ongoing randomized trials and for other clinical applications, such as cancer care [2]. Our interest in AA stability pertains to an ongoing randomized trial in sepsis [6], in which a dose of 50 mg/kg of AA is administered intravenously every 6 h for 96 h [6]. If this dose is diluted in a 50 mL minibag, a 50 kg patient receiving a single dose of 2.5 g would have a concentration of 36.8 mg/mL or

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