Lebrun John, Hecq Jean-Daniel, Vanbeckbergen Danielle, Jamart Jacque, Galanti Laurence M
Medical Laboratory.
Int J Pharm Compd. 2004 Mar-Apr;8(2):156-9.
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 100mg of tramadol/100mL of 5% dextrose was studied after the solution was frozen for 4 months at -20 deg C, followed by thawing in a microwave oven with a validated cycle and final storage at 4 deg 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 bufer pH 2.5 and ultraviolet detecion 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 frozen in advance by a centralized intravenous admixture service, then thawed before use in clinicl units.
盐酸曲马多（痛力克）常用于为住院患者进行静脉输注，以处理或预防需要阿片类水平镇痛的急性或慢性疼痛。提前配制盐酸曲马多静脉溶液可能有助于提高质量保证、时间管理和药物输送的成本节约；但对于其冷冻后经微波解冻的稳定性知之甚少。本研究的目的是调查冷冻、长期储存和微波解冻如何影响曲马多在5%葡萄糖输注液中的稳定性。研究了五个装有100mg曲马多/100mL 5%葡萄糖溶液的聚氯乙烯袋，溶液在-20℃冷冻4个月后，在经过验证的微波周期中解冻，并最终在4℃储存。采用反相柱，流动相为pH 2.5的磷酸盐缓冲液中含30%乙腈，在230nm处进行紫外检测，通过高效液相色谱法测定曲马多浓度。还进行了外观检查和pH测量。未观察到颜色变化或沉淀。曲马多至少60天稳定。在此期间，浓度-时间曲线估计回归线的置信下限保持在初始浓度的90%以上。在该稳定期内，pH值略有下降，但不影响色谱参数。在这些限制范围内，5%葡萄糖输注液中的曲马多可由集中式静脉药物配置服务提前冷冻配制，然后在临床科室使用前解冻。
