Cooper James F, Petry Neil A, Engelbrecht Hendrik, Breslow Kenneth
Endotoxin Consulting, POB 9435, Greensboro, NC 27429-0435.
PDA J Pharm Sci Technol. 2012 May-Jun;66(3):214-20. doi: 10.5731/pdajpst.2012.00860.
Endotoxin indicators (EIs) and photometric bacterial endotoxin test (BET) assays were used to determine the capacity of alumina (Al(2)O(3)) for removing endotoxin from a parenteral solution. Fludeoxyglucose F 18 (FDG) Injection, USP, a radioactive imaging agent, is made daily at about 150 American sites for same-day administration. Each FDG synthesis unit contains a cartridge of alumina for removing a radiochemical impurity before delivery to the final product vial. Recognizing that alumina is a cationic adsorption medium, its capacity for removing endotoxin was challenged with purified endotoxin. A 2000 EU vial of an EI was reconstituted with water or FDG, vortex-mixed, and passed through a representative final product assembly consisting of an alumina cartridge with connecting tubing, a sterilizing membrane filter, and aseptic collection vial. In addition to sterilization, the filter removed alumina "fines" that are inhibitory to the BET because of adsorption of the positive control. Confirmation of labeled claim for each EI and measurement of endotoxin challenge eluates from a simulated FDG process were analyzed by valid kinetic chromogenic assays using a microplate reader and a cartridge reader. Overkill depyrogenation conditions were achieved, defined as greater than a 3 log endotoxin reduction. In conclusion, alumina was observed to depyrogenate the eluate of a representative FDG synthesis unit.
A fever-inducing (pyrogenic) bacterial toxin may arise during the complex synthesis of a radioactive imaging agent known as Fludeoxyglucose F 18 (FDG) Injection. One of the purification steps for FDG, a cartridge of aluminum oxide (alumina), removes negatively charged, radioactive impurities. Representative FDG solutions were inoculated with purified bacterial endotoxin to determine if the toxin's negative charge would result in removal by alumina. Alumina's effectiveness for endotoxin removal, a process known as depyrogenation, was measured by endotoxin detection assays. Alumina reduced endotoxin levels by more than a thousand fold in a simulated FDG process. Therefore, an unrecognized benefit of the alumina cartridge is removal of a potentially harmful toxin while purifying the FDG for patient injection.
使用内毒素指示剂（EI）和光度法细菌内毒素检测（BET）测定法来确定氧化铝（Al₂O₃）从肠胃外溶液中去除内毒素的能力。氟脱氧葡萄糖F 18（FDG）注射液，美国药典，一种放射性成像剂，在美国约150个地点每天制备以供当日给药。每个FDG合成单元都包含一个氧化铝柱，用于在输送到最终产品小瓶之前去除一种放射化学杂质。认识到氧化铝是一种阳离子吸附介质，用纯化的内毒素对其去除内毒素的能力进行了挑战。将一瓶2000 EU的EI用纯水或FDG复溶，涡旋混合，然后通过一个代表性的最终产品组件，该组件由一个带有连接管的氧化铝柱、一个除菌膜过滤器和无菌收集小瓶组成。除了除菌外，过滤器还去除了由于吸附阳性对照而对内毒素检测有抑制作用的氧化铝“细粉”。通过使用酶标仪和柱式读数仪的有效动力学显色测定法，分析了每个EI标记声明的确认情况以及模拟FDG过程中内毒素挑战洗脱液的测量结果。实现了过度杀灭去热原条件，定义为内毒素减少超过3个对数。总之，观察到氧化铝可使代表性FDG合成单元的洗脱液去热原。
在一种名为氟脱氧葡萄糖F 18（FDG）注射液的放射性成像剂的复杂合成过程中，可能会产生一种引起发热（热原性）的细菌毒素。FDG的纯化步骤之一，一个氧化铝柱，可去除带负电荷的放射性杂质。用纯化的细菌内毒素接种代表性的FDG溶液，以确定毒素的负电荷是否会导致被氧化铝去除。通过内毒素检测测定法测量了氧化铝去除内毒素的有效性，这一过程称为去热原。在模拟的FDG过程中，氧化铝将内毒素水平降低了一千多倍。因此，氧化铝柱的一个未被认识到的好处是在纯化用于患者注射的FDG时去除了一种潜在有害的毒素。
