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Effect of Freezing, Long-Term Storage and Microwave Thawing on the Stability of Tramadol in 5% Dextrose Infusion in Polyvinyl Chloride Bags

Author(s):  Lebrun John, Hecq Jean-Daniel, Vanbeckbergen Danielle, Jamart Jacques, Galanti Laurence M

Issue:  Mar/Apr 2004 - Overview of USP Chapter <797>
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Abstract:  Tramadol hydrochloride (Contramal) is often used as infusions for hospitalized patients to manage or prevent acute or chronic pain that requires analgesia at opioid level. Advance preparation of intravenous solutions of tramadol hydrochloride could be useful to improve quality assurance, time management and cost savings of drug delivery; but little is known about their stability after freezing followed by microwave thawing. The purpose of this study was to investigate how freezing, long-term storage and microwave thawing can affect the stability of tramadol in 5% dextrose infusion. The stability of five polyvinyl chloride bags of solution containing 100 mg of tramadol/100 mL of 5% dextrose was studied after the solution was frozen for 4 months at -20°C, followed by thawing in a microwave oven with a validated cycle and final storage at 4°C. Concentration of tramadol was measured by high-performance liquid chromatography using a reversed-phase column, a mobile phase consisting of 30% acetonitrile in phosphate buffer pH 2.5 and ultraviolet detection at 230 nm. Visual inspection and pH measurement were also performed. No color change or precipitation was observed. Tramadol was stable for at least 60 days. Throughout this period, the lower confidence limit of the estimated regression line of the concentration-time profile remained at above 90% of the initial concentration. During this stability period, the pH value decreased slightly without affecting chromatographic parameters. Within these limits, tramadol in 5% dextrose infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.

Related Keywords: Galanti, Laurence M, PhD, MD, Hecq, Jean-Daniel, Jamart, Jacques, MD, Lebrun, John, Tramadol, effect of freezing on stability, Tramadol, effect of long-term storage on stability, Tramadol, effect of microwave thawing on stability, Tramadol, for infusion, stability of, Vanbeckbergen Danielle


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