背景:为了评估复合芬太尼时的化学稳定性和物理相容性,罗库溴铵,和阿托品以固定的比例支持胎儿介入和手术期间的肌内给药。
方法:高度浓缩的芬太尼组合,罗库溴铵,阿托品是根据产妇胎儿护理中心的常用处方制定的。使用液相色谱-质谱(LC/MS-MS)完成化学稳定性测试,以检测和定量阿托品,罗库溴铵,还有芬太尼,芬太尼-d5是6-的内标,12、24-,以及样品制备后36小时。使用美国药典(USP)<788>推荐的光遮蔽(LO)分析技术以及在样品制备后6小时和24小时的新型背膜成像(BMI)完成物理相容性测试。使用两种技术的USP<788>颗粒计数极限确定物理相容性。
结果:基于LC/MS-MS结果,在所有测试时间点,样本均保持预期的药物浓度.对于物理兼容性测试,根据USP<788>大体积颗粒计数阈值,两种方法在6小时时颗粒计数均符合被视为相容的标准,但在24小时时超过了容许阈值.
结论:罗库溴铵的组合,芬太尼,和阿托品用于肌内胎儿给药在6小时内是物理相容和化学稳定的。
BACKGROUND: The aim of the study was to evaluate chemical stability and physical compatibility when combining fentanyl, rocuronium, and atropine in a fixed ratio to support intramuscular drug delivery during fetal intervention and surgery.
METHODS: A highly concentrated combination of fentanyl, rocuronium, and atropine was created based on common prescribing practices at a maternal-fetal care center. Chemical stability testing was completed using liquid chromatograph mass spectrometry-mass spectrometry (LC/MS-MS) to detect and quantitate atropine, rocuronium, and fentanyl, with fentanyl-d5 being an internal standard at 6, 12, 24, and 36 h following sample preparation. Physical compatibility testing was completed using United States Pharmacopeia (USP) <788> recommended analytical technique of light obscuration in addition to novel backgrounded membrane imaging at 6 and 24 h following sample preparation. Physical compatibility was determined using USP <788> particle count limits for both techniques.
RESULTS: Based on LC/MS-MS results, the samples retained expected medication concentrations at all time points tested. For physical compatibility testing, the particle counts met criteria to be considered compatible per USP <788> large-volume particle count thresholds at 6 h by both methods but exceeded tolerable thresholds at 24 h.
CONCLUSIONS: The combination of rocuronium, fentanyl, and atropine for intramuscular fetal administration is physically compatible and chemically stable for 6 h.