地塞米松磷酸钠注射液仿制制剂与原研制剂有关物质比较

Comparison of Related Substances Between the Generic and Original-Patented Dexamethasone Sodium Phosphate Injection

目的建立检测地塞米松磷酸钠注射液中有关物质的高效液相色谱法,比较仿制制剂和原研制剂的质量差异。方法色谱柱为Kromasil C_(8)柱,流动相A为0.1 mol/L乙酸铵溶液(用乙酸调pH至3.8)-甲醇(65∶35,V/V),流动相B为0.1 mol/L乙酸铵溶液(用乙酸调pH至4.0)-甲醇(30∶70,V/V),梯度洗脱,流速为1.0 mL/min,检测波长为254 nm。结果地塞米松磷酸钠与7个已知杂质A-G分离良好,质量浓度在0.596~11.916μg/mL范围内与峰面积线性关系良好(r=0.9994)。变更处方后,不再添加抗氧剂亚硫酸钠,不再检出杂质Ⅰ。仿制制剂中已知杂质、未知杂质的数量和含量均与原研制剂相当。结论该方法操作简单、重复性好、专属性强,可用于地塞米松磷酸钠注射液的杂质检查,保障仿制制剂质量不劣于原研制剂。

Objective To establish a high-performance liquid chromatography(HPLC)method for the determination of related substances in Dexamethasone Sodium Phosphate Injection,and to compare the quality differences between the generic and original-patented preparations.Methods The chromatographic column was Kromasil C_(8) column,the mobile phase A was 0.1 mol/L ammonium acetate solution(adjusted to pH 3.8 with acetic acid)-methanol(65∶35,V/V),the mobile phase B was 0.1 mol/L ammonium acetate solution(adjusted to pH 4.0 with acetic acid)-methanol(30∶70,V/V),the elution method was gradient elution,the flow rate was 1.0 mL/min,and the detection wavelength was 254 nm.Results Dexamethasone sodium phosphate was well separated from seven known substances(impurity A-impurity G),and its linear range was 0.596-11.916μg/mL(r=0.9994).After the prescription was changed with no adding antioxidant sodium sulfite,the impurityⅠin the preparation was not detected.The quantities and contents of known and unknown impurities in the generic preparation were similar to those in the original-patented preparation.Conclusion The method is simple,repeatable and specific,which can be used for the impurity detection of Dexamethasone Sodium Phosphate Injection to ensure that the quality of generic preparation is not inferior to that of the original-patented preparation.