Compatibility and stability of binary mixtures of ketorolac tromethamine and tramadol hydrochloride injection concentrate and diluted infusion solution.
OBJECTIVE
Ketorolac added to tramadol as an injection mixture convenient for clinical use has been shown to be an effective balanced analgesic regimen in alleviating moderate-to-severe pain. However, analytical confirmation of the compatibility and stability of this combination is not available. This study examined the compatibility and stability of this combination.


METHODS
Two different mixtures containing ketorolac tromethamine and tramadol hydrochloride were examined: ketorolac (10 mg/mL) and tramadol (33.3 mg/mL) prepared as injection concentrate in ampoule mingled together in the ratio of one ampoule to one ampoule; diluted ketorolac (2 mg/mL) and tramadol (20 mg/mL) prepared in saline infusion solution, with or without pH adjustment. The mixtures were visually inspected for precipitation and color change. Quantitative chemical analysis was performed on days 0, 1, 3 and 7 by high-performance liquid chromatography.


RESULTS
When stored at room temperature under ambient light, the ketorolac (10 mg/mL)-tramadol (33.3 mg/mL) injection concentrate and ketorolac (2 mg/mL)-tramadol (20 mg/mL) solution, without pH adjustment and adjusted to pH 5-8, were physico-chemically stable, and neither visible precipitation nor loss of concentration was found. With the ketorolac (2 mg/mL)-tramadol (20 mg/mL) solution adjusted to pH 9, however, precipitation occurred immediately, resulting in a significant loss of tramadol.


CONCLUSIONS
This study suggests that a ready-to-use ketorolac-tramadol mixture, either undiluted or diluted in physiological saline solution, can be prepared, with a shelf life of at least 7 days when stored at room temperature under ambient light.
Lin
Tzu-Fu
TF
Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Lin
Feng-Sheng
FS
Chou
Wei-Han
WH
Yeh
Yu-Chang
YC
Lin
Chih-Peng
CP
Fan
Shou-Zen
SZ
Sun
Wei-Zen
WZ
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D007263:Infusions, Parenteral; D020911:Ketorolac Tromethamine / Q000008:administration & dosage*; D012965:Sodium Chloride; D014147:Tramadol / Q000008:administration & dosage*
D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D014147:Tramadol; D012965:Sodium Chloride; D020911:Ketorolac Tromethamine