院内製剤中のエンドトキシン測定と荷電フィルタの性能評価

抄録

The prevention of endotoxin (ETX) contamination is important for manufacturing injections. As a result, the concentration of ETX in injections has been recently regulated in the Japanese Pharmacopoeia. In this study, ETX in 8 injections prepared at a hospital pharmacy were measured and the removal of ETX by filtration using a charged membrane filter (CMF) made of Nylon 66 (Zetapor^®, CUNO) was evaluated. ETX was automatically measured with a Limulus test employing a turbidmetric kinetic assay (Toxinometer^®, WAKO). ETX in H₂SeO₃ and MnCl₂ injections were measured without dilution but others need to be diluted to eliminate any interference with the reaction. In particular, the ZnSO₄ injection was diluted 2000 times. In the preparations, only 1 % indigocarmin injection showed 0.311 EU/mL of ETX.
In a preliminary evaluation, CMF removed ETX completely in the non-electrolytic solutions such as glucose. However, in electrolytic solutions like NaCl, the filtration efficiency of CMF was suggested to decrease by some factors such as the concentration of electrolytes, the pH of the solution and the origin of ETX. In 0.9% NaCl solution to which the control standard ETX was added, the recovery rate of ETX using CMF was 0.3-2%. In 10% NaCl solution, the recovery rate was 37-47% under the same conditions, but it became 75-79% when another origin of ETX was added. In the actual process of preparations, ETX was found in 1 % indigocarmin injection, but it was not found in them when CMF was used. ETX was not removed by a usual filter membrane without any charging and not inactivated completely by steam sterilization. Therefore, filtration using CMF was found to effectively remove ETX together with steam sterilization.
Filtration using CMF is thus considered to be a simple and effective method for maintaining a good quality of injections prepared at hospital pharmacies.