泛昔洛韦有关物质检查方法的验证与优化

Validation and optimization of the method for the detection of related substances of famciclovir

目的对某企业参照USP43建立的泛昔洛韦有关物质检测方法进行色谱条件、方法专属性、杂质校正因子、杂质相对保留时间、最低检出限、进样精密性、稳定性等方面的验证与优化。方法采用高效液相色谱法洗脱,色谱柱:Agilent Eclipse XDB-C_(8)(4.6 mm×150 mm,5μm),流速:1.5 ml/min,进样体积:20μl;中国药典2020年版方法:采用C_(18)-HPLC等度洗脱法,以乙腈:0.02 mol/L磷酸盐缓冲液(20∶80)为流动相,检测波长221 nm;某企业自拟方法:以乙腈(乙腈浓度从5%~30%)-0.02 mol/L磷酸盐缓冲液(pH值4.00±0.05)为流动相进行梯度洗脱,检测波长220 nm。结果该方法专属性良好;泛昔洛韦杂质A检出限为17.6 ng/ml,泛昔洛韦杂质B检出限为16.8 ng/ml;进样精密性良好;稳定性良好,建议将该企业自拟方法流动相中的缓冲溶液的pH值修改为3.50。结论该方法快速、简便,可用于泛昔洛韦原料药的有关物质检测,同时为企业在制定杂质控制限度时提供依据。

Objective To verify and optimize the chromatographic conditions,method specificity,impurity correction factor,impurity relative retention time,minimum detection limit,injection precision,stability and other aspects of the detection of related substances of famciclovir established by a company with reference to USP43.Methods A HPLC method was used with a Agilent Eclipse XDB-C_(8) column 4.6 mm×150 mm(5μm),the flow rate was 1.5 ml/min and the injection volume was 20μl.A C_(18) HPLC isocratic elution method of Chinese Pharmacopoeia 2020 edition was used.The mobile phase was acetonitrile:0.02 mol/L phosphate buffer(20∶80),the detection wavelength was 221 nm.The mobile phase of enterprise self-designed method was acetonitrile(acetonitrile concentration from 5%to 30%)-0.02mol/L phosphate buffer(pH 4.00±0.05)with gradient elution,the detection wavelength was 220 nm.Results The method has good specificity.The detection limits of impurity A and B of famciclovir were 17.6 ng/ml and 16.8 ng/ml respectively.The method has good sampling precision,and the stability is good,it is recommended to modify the pH value of buffer solution in the mobile phase of the self-designed method to 3.50.Conclusion The method is rapid and simple,and can be used for the detection of related substances of famciclovir in bulk.At the same time,it provides a basis for enterprises to set the impurity control limit.