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Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl

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A low dose solution of adrenaline 2 μg · ml-1, fentanyl 2 μg · ml-1 and bupivacaine 1 mg · ml-1 has been reported to give superior pain control when used for epidural analgesia after major surgery. The present paper describes the compounding and chemical stability of this triple-component solution during storage and use.


Sterile triple-component concentrates (11X) were diluted by the use of gas isolator technology to give ready-to-use infusion solutions. Eight solutions were analysed by reverse phase high-performance liquid chromatography (HPLC) methods, and assays were performed on 1, 45, 90 and 180 days after storage at 2–8°C. After 180 days the solutions were subsequently stored at 22°C for four days before they were reanalysed. HPLC quantification of adrenaline was also performed on samples from solutions given to 28 different patients.


The concentration of adrenaline and fentanyl decreased approximately 3.5% from 1 to 180 days at 4°C and four days at 22°C. The corresponding figure for bupivacaine was an apparent increase by 2.4% in concentration. No absorption to the polypropylene plastic bags of fentanyl and bupivacaine was detected. None of the 28 samples derived from used infusion bags contained less than 95% of the declared content of adrenaline.


The triple-component epidural analgesic solution remained stable during six months of cold storage, followed by four days of storage at room temperature. No significant degradation of adrenaline was observed in infusion solutions returned from the wards.

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Keywords: Analgesia, epidural; adrenaline; bupivacaine; drug stability; fentanyl

Document Type: Original Article

Affiliations: The National Hospital Pharmacy, and Department of Anaesthesiology, The National Hospital (Rikshospitalet), Oslo, Norway

Publication date: 2000-08-01

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