头孢氨苄、头孢拉定原料中残留2-萘酚的控制

目的: 探讨对头孢氨苄、头孢拉定原料中增加2-萘酚检查的必要性,建立科学、合理的2-萘酚检查方法以及限度。 方法: 采用HPLC-UV法,C₁₈(4.6 mm×250 mm,5 μm)色谱柱,以甲醇-水(55∶45)为流动相,流速为1.0 mL·min^-1;检测波长为225 nm,分析20批头孢氨苄原料、2批头孢拉定原料以及217批头孢氨苄片(胶囊)、380批头孢拉定胶囊中含2-萘酚的量,并进行方法学验证。 结果: 方法专属性强、线性范围宽、精密度好、准确度高、耐用性好,超过50%的样品含有不同量的2-萘酚,有些企业样品中含量较大,同一企业样品批间差异较大;根据当前ICH指导原则以及已发表的文献资料,初步确定了头孢氨苄、头孢拉定原料中2-萘酚的限度。 结论: 建议在中国药典头孢氨苄、头孢拉定原料中增加2-萘酚检查项并初步拟定了限度,其限度科学性、合理性需进一步验证。

Objective: To disscuss the necessity for establishing the quality control method for determining 2-naphthol in cefalexin and cefradine raw substance and building a scientific and reseanable test method and specification limit for 2-naphthol. Methods: Analyzed the content of 2-naphthol in 20 lots of cefalexin raw substance,2 lots of cefradine raw substance,217 lots of cefalexin tablets/capsule and 380 lots of cefradine capsules using by a HPLC-UV method which was equipped with a C₁₈ (4.6 mm×250 mm,5 μm) column and using a mixture of methanol-water (55∶45) as mobile phase and the flow rate was 1.0 mL·min^-1 and the detection wavelength was 225 nm.The method was validated adequeatly. Results: The HPLC method is specific,linear,accurate,precise and robust.More than 50% medicine samples(drug substance and drug product)contain different content of 2-naphthol and some samples contain a great quantity of 2-naphthol.There were significant differences between different batches from the same company.The specification limits of 2-naphthol in cefalexin and cefradine drug substance monograph were initially built according to the current ICH guidelines and published literatures. Conclusions: Suggestion establishing the control method for determining 2-naphthol in cefalexin and cefradine drug substance in Chinese Pharmacophia monograph containing the specification limits which need more validating scientifically and reseanably by future literatures.