重组C因子法检测福沙匹坦二葡甲胺中细菌内毒素的方法学研究

目的 建立福沙匹坦二葡甲胺的细菌内毒素检测方法。方法 使用凝胶法、动态显色法、重组C因子法对福沙匹坦二葡甲胺进行方法学研究。结果 凝胶法在检测浓度范围内结果均为阳性结果,不符合凝胶法进行干扰实验的前提。动态显色法中,出现了不同稀释倍数回收率符合药典规定的情况下,内毒素检测结果差异极大（结果差异>200倍）,使用了抗增液仍存在该问题。重组C因子法中,当样品浓度<0.062 5 mg·mL^-1即不存在干扰作用并且不存在上述问题,结果符合规定。结论 福沙匹坦二葡甲胺无法使用经典的凝胶法和动态显色法进行内毒素检测。重组C因子法经过方法学研究,可以用于福沙匹坦二葡甲胺的内毒素质量控制。

Methodological Study on the Detection of Bacterial Endotoxin in Fosaprepitant Dimeglumine by Recombinant Factor C

OBJECTIVE To establish a bacterial endotoxin test method for fosaprepitant dimeglumine. METHODS The methodological study of fosaprepitant dimeglumine was carried out by gel colt method, dynamic chromogenic method and recombinant factor C method. RESULTS The result of gel colt method was positive in the range of detection concentration, which did not meet the premise of the gel colt method for interference experiments. In the dynamic chromogenic method, when the recovery ratio of different dilution multiples met the requirements of the pharmacopoeia, the endotoxin detection results were extremely different(the difference was greater than 200 times), and the problem still existed with the use of endotoxin-specific buffer. When the sample concentration was lower than 0.062 5 mg·mL^-1, there was no interference existed, and the results were in compliance with the regulations using recombinant factor C method. CONCLUSION It is not possible to detect endotoxin in fosaprepitant dimeglumine by classical gel method and dynamic chromogenic method. The recombinant factor C method can be used for the endotoxin quality control of fosaprepitant dimeglumine based on the methodology research.