泛昔洛韦制剂中有关物质的探索性研究

An investigation of related substances in famciclovir preparations

目的:完善《中国药典》2020年版二部泛昔洛韦片剂和胶囊剂质量标准,建立HPLC法对有关物质进行测定,考察有关物质的影响因素。方法:采用UHPLC-MS/MS法对有关物质进行初步推断,并采用Aglient ZORBAX SBC_(18)(4.6 mm×250 mm,5μm)色谱柱,以0.02 mol·L^(-1)磷酸二氢钾为流动相A,乙腈为流动相B,进行梯度洗脱。结果:初步推断了已知杂质和3个未知杂质;高温高湿条件下,有2家胶囊剂企业的有关物质升高较快,经确认水分增加是主要的影响因素。结论:本研究可满足对泛昔洛韦制剂有关物质的检验需求,加强对泛昔洛韦制剂的安全性和有效性的控制,并为各企业产品的储存条件提供参考。

Objective:To improve the monographs of famciclovir tablets and capsules in the Chinese Pharmacopoeia 2020 VolⅡ,to establish an HPLC method for determination of the related substances in famciclovir tablets and capsules and to investigate the influencing factors.Methods:The related substances were identified by UHPLC-MS/MS.The chromatographic separation was performed in an Aglient ZORBAX SBC_(18) column(4.6 mm×250 mm,5μm)under the gradient elution of 0.02 mol·L^(-1) potassium dihydrogen phosphate solution(mobile phase A)and acetonitrile(mobile phase B).Results:The known impurities and three unknown impurities were identified.Under the condition of high temperature and humidity,the related substances in famciclovir capsules from two manufacturers rapidly increased.It was confirmed that the increase of moisture was the main influencing factor.Conclusion:This study can meet the requirements on determination of the related substances in famciclovir preparations,improve the safety and efficacy of famciclovir preparations,and provide a recommendation for the storage conditions.