达沙替尼原料中的杂质研究

Impurities in raw material of dasatinib

目的:建立达沙替尼原料药中杂质的研究方法,为评价达沙替尼原料药的优劣提供依据。方法:采用C18柱,以5 mmol·L-1甲酸溶液-乙腈-甲醇(88∶6∶6)为流动相A,5 mmol·L-1甲酸溶液-乙腈-甲醇(10∶85∶5)为流动相B,梯度洗脱;采用LC/MS技术对达沙替尼原料中的4个杂质进行了鉴定,并对4个杂质进行了全合成。结果:所建立的LC/MS条件下,达沙替尼及其杂质可得到有效的分离;通过合成杂质对照品和结构确证,证明原料药中含该4种杂质。结论:利用LC/MS技术可检测达沙替尼及其杂质的结构,且本方法快速、灵敏、专属性高。

Objective： To establish a method for determination of impurities in raw material of dasatinib, and to provide evidence for evaluation of dasatinib qualities. Methods： Four kinds of the impurities in dasatinib were identified using a C18 column by LC/MS. The mobile phase A was 5 mmol.L-1 formic acid solution-acetoni- trile-methanol （88： 6： 6）, mobile phase B was 5 mmol.L-1 formic acid solution-acetonitrile-methanol （10： 85： 5）, and gradient elution was applied. Furthermore, the 4 impurities were synthesized. Results ： Under the LC/MS con- ditions, dasatinib and its impurities were effectively separated. To prove the contained impurities, their retention times were compared with those of the respective synthetic references as well as by structural elucidation of the im- purity. Conclusion： The method based on LC/MS for identification of dasatinib and its impurities has been suc- cessfully established, which is rapid, sensitive and specific.