目的 提出一类生物标准物质稳定性分析的加权最小二乘方法。方法 根据Arrhenius或者Eyring方程和化学反应原理,在适当的假设条件下,建立拟合测试温度下的降解速率常数k的数学模型。通过求解该模型,预测在正常条件下生物标准物质的稳定性情况。结果 根据蛋白质药品重组人粒细胞集落刺激因子(G-csf)和干扰素α-2a的稳定性实验数据,进行了热加速降解分析,数值实验表明该分析方法可行。结论 该分析方法可为生物药物的稳定性和有效期预测提供理论依据。

OBJECTIVE To establish a weighted least square method for the accelerated degradation analysis of protein-type biological standard substances.METHODS A mathematical model was proposed to estimate the parameters of degradation rate constants k at the elevated temperatures based on the Arrhenius or Eyring equation and chemical reaction principles under the suitable assumptions. Hence, it is probably to predict the stability of biological standard at the normal condition by solving the model.RESULTS According to the experimental data of recombinant human granulocyte colony-stimulating factor and interferon α-2a, the preliminary numerical experiments were also performed and the results confirm the reliability of the method in the paper.CONCLUSION The same methodology may be applied in the pharmaceutical industry where it is necessary to predict the viable shelf-life of biological products.