Department of Hospital Pharmacy, Hamamatsu University School of Medicine.
Department of Pharmacy, Iwata City Hospital.
Biol Pharm Bull. 2019;42(12):2062-2068. doi: 10.1248/bpb.b19-00537.
Dacarbazine (DTIC) is converted to the photo-degradation product 4-diazoimidazole-5-carboxamide (Diazo-IC) by light. Diazo-IC production is often responsible for the pain reactions observed during peripheral intravenous infusion of DTIC in clinical settings. Although light shielding during infusion decreases the photo-degradation of DTIC, its usefulness for the preparation of DTIC has not yet been fully clarified. The aim of this study was to investigate the light conditions during the preparation of DTIC solution in the compounding room from the viewpoint of the production amount of Diazo-IC. DTIC solution was prepared in the compounding room. Various light and temperature conditions and dissolving solutions during the preparation were investigated. The amounts of DTIC and Diazo-IC in solutions were determined using an HPLC coupled to UV detection. The photo-degradation of DTIC was estimated by the amount of Diazo-IC. Diazo-IC production in the dissolving solutions increased in a time-dependent manner at 4 and 25°C under light shielding. Light exposure during the dissolving process did not affect the DTIC and Diazo-IC concentrations. Light shielding during dissolution did not alter the Diazo-IC production until 4 h after dilution. In conclusion, short duration light exposure did not affect Diazo-IC production. These findings suggest that light shielding is not needed in the preparation of DTIC in the compounding room from the viewpoint of Diazo-IC production.
达卡巴嗪(DTIC)在光照下转化为光降解产物 4-重氮咪唑-5-甲酰胺(Diazo-IC)。在临床环境下经外周静脉输注 DTIC 时,观察到的疼痛反应通常是由 Diazo-IC 的产生引起的。尽管在输注过程中进行避光可以减少 DTIC 的光降解,但它在 DTIC 制备中的用途尚未完全阐明。本研究旨在从 Diazo-IC 生成量的角度研究复合室内制备 DTIC 溶液时的光照条件。在复合室内制备 DTIC 溶液。研究了制备过程中的各种光照和温度条件以及溶解溶液。使用 HPLC 结合 UV 检测法测定溶液中 DTIC 和 Diazo-IC 的含量。通过 Diazo-IC 的量来估计 DTIC 的光降解。在避光条件下,4°C 和 25°C 下,Diazo-IC 的生成量随时间呈时间依赖性增加。在溶解过程中暴露于光线下不会影响 DTIC 和 Diazo-IC 的浓度。避光溶解直到稀释后 4 小时才会改变 Diazo-IC 的生成量。总之,短时间的光照暴露不会影响 Diazo-IC 的生成。这些发现表明,从 Diazo-IC 生成的角度来看,在复合室内制备 DTIC 时不需要避光。