盐酸地芬尼多片的有关物质分析

Analysis of related substances in Difenidol Hydrochloride Tablets

目的对国内上市的盐酸地芬尼多片与原研片的有关物质进行对比分析。方法采用《中华人民共和国药典》2015版二部收载的盐酸地芬尼多片有关物质测定方法,对其进行测定,同时结合强制降解试验对比分析其有关物质情况。结果杂质Ⅰ的检出限为2.8 ng,定量限为9.7 ng;盐酸地芬尼多溶液在18 h内稳定,各杂质及主峰峰面积相对标准偏差(RSD)均<2%;杂质Ⅰ质量浓度在0.4829~48.2900μg/ml范围内与峰面积线性良好(R2=1);杂质Ⅰ精密度试验,峰面积RSD为4.2%(n=12);杂质Ⅰ平均回收率(n=6)为102.6%,RSD为2.0%;国内首仿厂家的两批次片剂未检出杂质,另一批检出已知杂质Ⅰ,含量为0.14%;原研厂家两批次未检出杂质,另一批检出杂质Ⅰ,含量为0.10%;其他三个厂家的片剂均检出杂质Ⅰ,含量在0.2%~0.5%内。国内首仿厂家与原研厂家片剂在光照、氧化、热及碱破坏条件下有关物质均无显著变化,在酸破坏条件下主峰降解明显,降解15%,杂质Ⅰ增加15%。结论国内首仿厂家与原研厂家片剂有关物质一致,且在强制降解试验中杂质降解行为一致;另三家企业片剂的已知杂质Ⅰ含量较原研厂家偏高2~5倍。

Objective To evaluate the consistency of related substances between the domestically marketed Difenidol Hydrochloride Tablets and reference preparations.Methods The related substances of Difenidol Hydrochloride Tablets were determined and evaluated according to the official quality standard recorded in Pharmacopoeia of the People′s Republic(2015 edition,version 2).The forced degradation test was also carried out.Results The detection limit of impurityⅠwas 2.8 ng,and the quantitative limit was 9.7 ng.The solution of Difenidol Hydrochloride was stable in 18 hours,and the relative standard deviation(RSD)of impurities and main peak area was less than 2%.The linearity range of impurityⅠwas 0.4829-48.2900μg/ml(R2=1).In the precision test of impurityⅠ,the RSD of peak area was 4.2%(n=12).The average recovery of impurityⅠ(n=6)was 102.6%,and RSD was 2.0%.No impurities were detected in two batch tablets of the first domestic manufacturer.The content of impuritiesⅠwas 0.14%in another batch.No impurities were detected in two batch tablets of the original manufacturer.The content of impuritiesⅠwas 0.10%in another batch.The content of impuritiesⅠwas among 0.2%-0.5%in the other three domestic manufacturers′tablets.Under the conditions of light,oxidation,heat and alkaline damage,there was no significant change in the related substances between the first domestic imitator and the original manufacturer′s tablets.Under the acid damage condition,the degradation of the main peak was 15%,and the increase of impurityⅠwas 15%.Conclusion Impurity profiling of the first generic preparations is consistent with the reference preparations.For other three domestic manufacturers,impurityⅠcontent is 2-5 times higher than that of the reference preparations.