Korean J Pain.  2025 Apr;38(2):103-115. 10.3344/kjp.24316.

Physicochemical stability of mixtures of nonsteroidal anti-inflammatory drugs such as ketorolac and diclofenac and antiemetics such as ondansetron and ramosetron: an in vitro study

• Lee CH

• KMID: 2566643
• DOI: http://doi.org/10.3344/kjp.24316

Abstract

Background
Drugs administered intravenously during the postoperative period can mix before entering the bloodstream. This study assessed the stability of mixtures of non-steroidal anti-inflammatory drugs (ketorolac and diclofenac) and antiemetics (ondansetron and ramosetron) to determine their suitability for concurrent administration.
Methods
Ketorolac or diclofenac was combined with ondansetron or ramosetron at a 1:1 volume ratio. Each mixture was stored in a propylene syringe at 24°C for 2 hours. The mixtures were assessed visually, and the pH was measured. Additionally, the drug concentrations were determined using high-performance liquid chromatography (HPLC).
Results
Mixtures of ketorolac or diclofenac and ramosetron showed no crystal formation or pH changes, and HPLC analysis confirmed that the drug concentrations remained stable. In contrast, mixtures of ketorolac or diclofenac and ondansetron exhibited the visible formation of 10–50 μm crystals under a microscope. However, there were no changes in the pH levels, and HPLC analysis indicated that the drug concentrations remained stable for both the mixtures.
Conclusions
Mixtures of ketorolac or diclofenac and ramosetron demonstrated physical and chemical stability for up to 2 hours, indicating that their concurrent use is feasible. Conversely, mixtures of ketorolac or diclofenac and ondansetron should be avoided due to the formation of crystals, even though the concentration of each drug remained stable.

Keyword

Chromatography; High Pressure Liquid; Crystallization; Diclofenac; Drug Stability; Ketorolac; Ondansetron