Ensom Mary H H, Decarie Diane, Leung Karen, Montgomery Carolyne
, PharmD, FASHP, FCCP, FCSHP, FCAHS, is Professor and Director, Doctor of Pharmacy Program, Faculty of Pharmaceutical Sciences, and Distinguished University Scholar, The University of British Columbia; and Clinical Pharmacy Specialist, Department of Pharmacy, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia. She is also the Editor of CJHP.
Can J Hosp Pharm. 2009 Mar;62(2):112-8. doi: 10.4212/cjhp.v62i2.439.
To evaluate the stability of mixtures of hydromorphone and ketamine in 0.9% sodium chloride (normal saline [NS]) after storage for up to 7 days at room temperature (25°C).
The stability of 3 standard mixtures of hydromorphone and ketamine (hydromorphone 0.2 mg/mL + ketamine 0.2 mg/mL, hydromorphone 0.2 mg/mL + ketamine 0.6 mg/mL, and hydromorphone 0.2 mg/mL + ketamine 1.0 mg/mL) in NS was studied. Portions of each mixture were transferred to 3 brown glass bottles (100 mL), 3 plastic syringes (50 mL), and 3 IV bags (50 mL), which were then stored at room temperature (25°C). Physical characteristics, including pH, colour, and precipitation, were evaluated daily. Three 1.5-mL samples were collected from each bottle, syringe, and IV bag at baseline, at 24, 48, and 72 hours, and on day 7. Samples were analyzed in triplicate by a stability-indicating high-performance liquid chromatography method. Solutions were considered stable if they maintained 90% of the initial concentration of each drug. Samples from syringes and IV bags were subjected to standard sterility testing by incubation for 5 days in an enriched culture media.
No notable changes in pH or colour were observed, and no precipitation occurred in any of the solutions. All formulations maintained more than 90% of the initial concentration of each drug on day 7. No bacterial growth was observed in any of the samples tested.
Mixtures of hydromorphone and ketamine were stable for up 7 days at 25°C, and the sterility of the preparations was maintained. Because stability alone does not guarantee efficacy, it is recommended that clinical studies be conducted to evaluate the pharmacokinetics and pharmacodynamics of these formulations.
评估氢吗啡酮与氯胺酮在0.9%氯化钠（生理盐水[NS]）中的混合液在室温（25°C）下储存长达7天后的稳定性。
研究了3种氢吗啡酮与氯胺酮的标准混合液（氢吗啡酮0.2 mg/mL + 氯胺酮0.2 mg/mL、氢吗啡酮0.2 mg/mL + 氯胺酮0.6 mg/mL以及氢吗啡酮0.2 mg/mL + 氯胺酮1.0 mg/mL）在生理盐水中的稳定性。将每种混合液的一部分转移至3个棕色玻璃瓶（100 mL）、3个塑料注射器（50 mL）和3个静脉输液袋（50 mL）中，然后在室温（25°C）下储存。每天评估包括pH值、颜色和沉淀在内的物理特性。在基线、24、48和72小时以及第7天，从每个瓶子、注射器和静脉输液袋中采集3个1.5 mL的样本。采用稳定性指示高效液相色谱法对样本进行一式三份分析。如果溶液保持每种药物初始浓度的90%，则认为其稳定。对注射器和静脉输液袋中的样本进行标准无菌测试，在富集培养基中培养5天。
未观察到pH值或颜色有明显变化，且任何溶液中均未出现沉淀。所有制剂在第7天均保持每种药物初始浓度的90%以上。在任何测试样本中均未观察到细菌生长。
氢吗啡酮与氯胺酮的混合液在25°C下可稳定保存7天，且制剂的无菌性得以维持。由于仅稳定性并不能保证疗效，建议进行临床研究以评估这些制剂的药代动力学和药效学。
