Xu Q A, Trissel L A, Martinez J F
Division of Pharmacy, University of Texas, MD Anderson Cancer Center, Houston, USA.
Ann Pharmacother. 1997 Mar;31(3):297-302. doi: 10.1177/106002809703100305.
To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 micrograms/mL in dextrose 5% and in sodium chloride 0.9% injection.
Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at -20, 4, 23, and 32 degrees C. Samples were removed immediately and at various times over 7 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC.
Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23, 32 degrees C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0-9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time.
When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 micrograms/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.
研究5%葡萄糖注射液和0.9%氯化钠注射液中1mg/mL及16mg/mL氟尿嘧啶与12.5μg/mL枸橼酸芬太尼的物理相容性和化学稳定性。
分别在5%葡萄糖注射液和0.9%氯化钠注射液中制备药物的测试溶液，一式三份，分别储存在-20℃、4℃、23℃和32℃。在第0天及7天内的不同时间点立即取出样品，并储存在-70℃直至分析。通过目视检查以及使用颜色校正比浊仪测量浊度来评估物理相容性；使用光散射粒子计数器测量颗粒含量。通过用稳定性指示高效液相色谱法重复测量测试溶液中每种药物的浓度来确定化学稳定性。
当在聚氯乙烯（PVC）容器中将枸橼酸芬太尼与氟尿嘧啶混合时，枸橼酸芬太尼迅速损失，在最初15分钟内损失约25%，在最初1小时内损失约50%。枸橼酸芬太尼的损失如此之快，以至于无法准确测定零时刻的含量。枸橼酸芬太尼的损失程度随时间增加，并且在较高温度（即23℃、32℃）下发生得更快。在24小时内，所有样品中的损失均达到70%或更多。在氟尿嘧啶混合液的高pH值（9.0 - 9.5）下，芬太尼迅速吸附到容器上。用氢氧化钠将PVC容器中枸橼酸芬太尼溶液（不含氟尿嘧啶）的pH值调至9也会导致迅速的吸附损失。当在聚乙烯容器中制备混合液时，未发生枸橼酸芬太尼的吸附。在所有温度下，氟尿嘧啶至少7天保持稳定。在任何时间，任何测试溶液的浊度或颗粒含量均未出现肉眼可见或亚可见变化。
当在5%葡萄糖注射液和0.9%氯化钠注射液中与1mg/mL及16mg/mL氟尿嘧啶混合时，12.5μg/mL枸橼酸芬太尼由于吸附到PVC容器上而迅速大量损失，使得混合后几分钟内该组合就不可接受。吸附是由于混合液的碱性pH值导致的，据推测，枸橼酸芬太尼与任何碱性足够强的药物混合时都可能发生这种情况。
