目的:探索药品包装材料中环氧乙烷残留量测定的通用方法。方法:采用气相色谱法,选择60 ℃平衡40 min的顶空条件,DB-VRX毛细管色谱柱进行测定,柱温为50 ℃恒温,载气流速1.5 mL·min-1。结果:所建立的色谱分析方法可对药包材中的干扰物乙醛进行有效分离,专属性好,在0.38~18.96 μg·mL-1范围内线性关系良好(r=0.999 8)。在低、中、高3个浓度水平的回收率为96.8%~109.9%,RSD为0.9%~5.1%。通过对产品浸提时间、温度的验证,给出了滴眼剂瓶、预灌封注射器等药包材产品环氧乙烷测定的通用顶空条件。测定结果表明,低密度聚乙烯滴眼剂瓶体、内盖、预灌封玻璃注射器组合件中环氧乙烷残留量分别为3.80、14.41和99.65 μg·g-1。结论:通过评价不同种类药包材产品的浸提条件,得到了科学合理的样品供试液制备方法,建立专属性良好的分析方法并能较科学地评价药品包装材料中环氧乙烷的残留量。
Objective: To explore a general method for determination of ethylene oxide residue in pharmaceutical packaging materials. Methods: Gas chromatography(GC) with DB-VRX capillary column was used to determine ethylene oxide residue. The headspace balance condition was 60 ℃ for 40 min, the column temperature was constantly on 50 ℃, and the carrier gas flow rate was 1.5 mL·min-1. Results: The established GC analysis method could effectively separate acetaldehyde in drug packaging materials with good specificity. The linearity of ethylene oxide was good at the range of 0.38-18.96 μg·mL-1 (r=0.999 8). The recoveries at low, medium and high additive levels were 96.8%-109.9% with RSDs between 0.9% and 5.1%. Through the verification of extraction time and temperature, the common headspace condition for the packaging materials, such as eye drops and prefilled syringes were discussed. The results showed that the residual amounts of ethylene oxide in the bottle, inside cap of low density polyethylene eye drops and glass prefilled syringe assembly were 3.80, 14.41 and 99.65 μg·g-1, respectively. Conclusion: By evaluating the extraction conditions of different kinds of pharmaceutical packaging materials, a scientific and reasonable sample preparation method was obtained, and a specific and good analysis method was established, which could scientifically evaluate the residual amount of ethylene oxide residue in pharmaceutical packaging materials.
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