Terryn Hélène, Vanhelleputte Jean-Paul, Maquille Aubert, Tilquin Bernard
Laboratory of Chemical and Physicochemical Analysis of Drugs (CHAM), Université Catholique de Louvain, CHAM 72.30, Avenue E. Mounier, 72, B- 1200, Brussels, Belgium.
Pharm Res. 2006 Sep;23(9):2141-8. doi: 10.1007/s11095-006-9053-y. Epub 2006 Aug 9.
To study the chemical modifications induced upon irradiation of solid human insulin at radiosterilization doses and investigate the influence of the absorbed dose on radiolysis.
Volatile radiolytic products were monitored by gas chromatography coupled with mass spectrometry (GC-MS) and non-volatile products by two different high performance liquid chromatography (HPLC) methods: the formation of higher molecular weight proteins was assessed by size exclusion liquid chromatography whereas assays for related compounds and chemical potency tests were carried out using reverse-phase HPLC-UV. Conformational changes were investigated by measurements of circular dichroism.
After gamma irradiation at 10 kGy, the recovery of insulin was 96.8%; higher molecular weight proteins accounted for 0.35% (relative peak area) and other related compounds (including A21 desamido insulin) represented 1.29%. No major structural changes and no volatile radiolytic compounds were detected.
Human insulin samples irradiated in the solid-state at 10 kGy (gamma rays) and 14 kGy (electron-beam) meet the European Pharmacopoeia requirements and can be considered as quite stable towards radiation from a chemical analysis viewpoint.
研究在辐射灭菌剂量下对固体人胰岛素进行辐照时所诱导的化学修饰，并研究吸收剂量对辐射分解的影响。
通过气相色谱-质谱联用（GC-MS）监测挥发性辐射分解产物，通过两种不同的高效液相色谱（HPLC）方法监测非挥发性产物：采用尺寸排阻液相色谱评估高分子量蛋白质的形成，而相关化合物的测定和化学效价测试则使用反相HPLC-UV进行。通过圆二色性测量研究构象变化。
在10 kGy的γ射线辐照后，胰岛素的回收率为96.8%；高分子量蛋白质占0.35%（相对峰面积），其他相关化合物（包括A21脱酰胺胰岛素）占1.29%。未检测到主要结构变化和挥发性辐射分解化合物。
在10 kGy（γ射线）和14 kGy（电子束）下固态辐照的人胰岛素样品符合欧洲药典要求，从化学分析的角度来看，可以认为对辐射相当稳定。
