Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl. 2000

I Kjønniksen, and J Brustugun, and G Niemi, and H Breivik, and E Anderssen, and W Klem
The National Hospital Pharmacy, The National Hospital (Rikshospitalet), Oslo, Norway.

BACKGROUND A low dose solution of adrenaline 2 microg x ml(-1), fentanyl 2 microg x ml(-1) and bupivacaine 1 mg x 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. METHODS 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 degrees C. After 180 days the solutions were subsequently stored at 22 degrees C for four days before they were reanalysed. HPLC quantification of adrenaline was also performed on samples from solutions given to 28 different patients. RESULTS The concentration of adrenaline and fentanyl decreased approximately 3.5% from 1 to 180 days at 4 degrees C and four days at 22 degrees 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D008027 Light That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range. Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D002045 Bupivacaine A widely used local anesthetic agent. 1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide,Bupivacain Janapharm,Bupivacain-RPR,Bupivacaina Braun,Bupivacaine Anhydrous,Bupivacaine Carbonate,Bupivacaine Hydrochloride,Bupivacaine Monohydrochloride, Monohydrate,Buvacaina,Carbostesin,Dolanaest,Marcain,Marcaine,Sensorcaine,Svedocain Sin Vasoconstr,Bupivacain RPR
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D004349 Drug Packaging Containers, packaging, and packaging materials for drugs and BIOLOGICAL PRODUCTS. These include those in ampule, capsule, tablet, solution or other forms. Packaging includes immediate-containers, secondary-containers, and cartons. In the United States, such packaging is controlled under the Federal Food, Drug, and Cosmetic Act which also stipulates requirements for tamper-resistance and child-resistance. Similar laws govern use elsewhere. (From Code of Federal Regulations, 21 CFR 1 Section 210, 1993) DRUG LABELING is also available. Drug Containers and Closures,Packaging, Drug,Drug Containers,Container, Drug,Containers, Drug,Drug Container,Drug Packagings,Packagings, Drug
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004356 Drug Storage The process of keeping pharmaceutical products in an appropriate location. Drug Storages,Storage, Drug,Storages, Drug
D004837 Epinephrine The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS. Adrenaline,4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol,Adrenaline Acid Tartrate,Adrenaline Bitartrate,Adrenaline Hydrochloride,Epifrin,Epinephrine Acetate,Epinephrine Bitartrate,Epinephrine Hydrochloride,Epinephrine Hydrogen Tartrate,Epitrate,Lyophrin,Medihaler-Epi,Acetate, Epinephrine
D005283 Fentanyl A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078) Phentanyl,Duragesic,Durogesic,Fentanest,Fentanyl Citrate,Fentora,R-4263,Sublimaze,Transmucosal Oral Fentanyl Citrate,R 4263,R4263
D000327 Adsorption The adhesion of gases, liquids, or dissolved solids onto a surface. It includes adsorptive phenomena of bacteria and viruses onto surfaces as well. ABSORPTION into the substance may follow but not necessarily. Adsorptions

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