辐照对去甲肾上腺素注射液含量变化的影响

Effect of irradiation on content of Norepinephrine Bitartrate Injection

目的建立HPLC测定重酒石酸去甲肾上腺素注射液中重酒石酸去甲肾上腺素含量的方法,考察重酒石酸去甲肾上腺素注射液经不同强度γ射线辐照后主药的含量变化。方法将同批号重酒石酸去甲肾上腺素注射液置60Co-γ射线放射原中,分别一次性接受1、2、4、8、16、25 kGy辐照剂量照射,以0.14%庚烷磺酸钠溶液(磷酸调节pH=3.0)-甲醇=65∶35为流动相,流速1 ml/min,检测波长286 nm,进样量20μl,测定重酒石酸去甲肾上腺素注射剂含量。结果 HPLC测定方法的线性范围5～25μg/ml(r=0.999 9);低、中、高浓度(8,10,12 mg/ml)的平均回收率分别为99.685%、96.366%、97.557%;日间(n=3)及日内精密度(n=3)均小于2%,重酒石酸去甲肾上腺素辐照后外观及澄明度没有明显变化,含量随辐照强度增加其含量显著下降(P<0.05),且吸收8kGy辐照剂量以上含量下降超出质量合格范围。结论所建方法可用于重酒石酸去甲肾上腺素注射液的含量测定,辐照对重酒石酸去甲肾上腺素注射液的稳定性有显著影响。

Objective To develop a high performance liquid chromatography（HPLC） method to analyze the content of norepinephrine bitartrate in Norepinephrine Bitartrate Injection,and study the content changes of the injection after exposure to γ-ray irradiation at different intensities.Methods Norepinephrine Bitartrate Injection of the same batch was under the exposure to 60Co-γ ray radiation at 1,2,4,8,16,and 25 kGy by one time.After that,0.14% heptanesulfonic acid sodium salt solution（pH value adjusted to 3.0 by using phosphate）： methanol（65∶35） as mobile phase,flow rate 1 ml/min,detection wavelength 286 nm,injection volume 20 μl were used to determinate the norepinephrine bitartrate content.Results The linear range of norepinephrine bitartrate was 5 to 25 μg/ml（r=0.999 9）.the yield rates at low,medium and high concentrations of norepinephrine bitartrate（8,10 and 12 μg/ml） was 99.685%,96.366%,and 97.557%,respectively.The inter-day（n=3） and intra-day precision（n=3） were less than 2%.The appearance and clarity of the Injection had no significant change,but the content of norepinephrine bitartrate was decreased in an irradiation dose-dependent manner（P0.05）.Especially,when the dose was above 8 kGy,and the content was even lower than the range of acceptable quality.Conclusion Our developed HPLC method can be used to determine the active ingredient content in Norepinephrine Bitartrate Injection.Irradiation has a significant impact on the stability of Norepinephrine Bitartrate Injection.