Marciniec B, Dettlaff K, Naskrent M
Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 60-780 Poznań, Grunwaldzka 6, Poland.
J Pharm Biomed Anal. 2009 Nov 1;50(4):675-8. doi: 10.1016/j.jpba.2008.08.032. Epub 2008 Sep 7.
The effect of ionising irradiation on the antifungal drug clotrimazole has been studied. The compound was subjected to ionisation irradiation in the form of high-energy electron beam (25-800 kGy) from an accelerator. Before and after the irradiation the compound was subjected to the EPR, TLC, HPLC and HPLC-MS analysis. After irradiation with doses 400-800 kGy the colour of the substance was changed from white to cream. Four products of radiolysis appeared in the HPLC chromatogram at 7.7, 4.2, 6.4 and 14.6 min and the active ingredient content decreased to 96.5%. The irradiation with a dose of 25 kGy resulted in the appearance of trace amounts of the product at 7.7 min and free radicals (2.54 x 10(14)spins/g). On the basis of the HPLC-MS data, the main product of radiolysis (t(R)=7.7 min) is 1-(9-phenylfluoren-9-yl)-imidazole. Besides traces of (2-chlorophenyl)-diphenylmethanol, other impurities listed in the European Pharmacopoeia (European Pharmacopea, 5th edition, Council of Europe, Strasbourg, France, 2004.) have not been detected. Clotrimazole has been found to show relatively high resistance to ionising irradiation (greater than fluconazole) and probably will be suitable for radiation sterilisation but with doses lower than 25 kGy.
已对电离辐射对抗真菌药物克霉唑的影响进行了研究。该化合物以来自加速器的高能电子束（25 - 800 kGy）形式接受电离辐射。辐射前后，该化合物进行了电子顺磁共振（EPR）、薄层色谱（TLC）、高效液相色谱（HPLC）和高效液相色谱 - 质谱（HPLC - MS）分析。用400 - 800 kGy剂量辐射后，物质颜色从白色变为米色。HPLC色谱图在7.7、4.2、6.4和14.6分钟出现了四种辐射分解产物，活性成分含量降至96.5%。25 kGy剂量的辐射导致在7.7分钟出现痕量产物和自由基（2.54×10¹⁴自旋/克）。根据HPLC - MS数据，辐射分解的主要产物（保留时间t(R)=7.7分钟）是1 -（9 - 苯基芴 - 9 - 基）-咪唑。除了痕量的（2 - 氯苯基）-二苯基甲醇外，未检测到《欧洲药典》（《欧洲药典》，第5版，欧洲委员会，法国斯特拉斯堡，2004年）中列出的其他杂质。已发现克霉唑对电离辐射表现出相对较高的抗性（高于氟康唑），可能适用于辐射灭菌，但剂量要低于25 kGy。
