盐酸西那卡塞潜在基因毒性杂质的合成、确证和检测

Synthesis,characterization and detection of potential genotoxic impurity of cinacalcet hydrochloride

目的合成盐酸西那卡塞原料药和制剂中的潜在基因毒性杂质间三氟甲基苯丙醛二聚体,完成结构确证,建立检测方法,并对盐酸西那卡塞原料药和制剂样品进行检测,提高对盐酸西那卡塞原料药和制剂的质量控制。方法以间三氟甲基苯丙醛为起始原料,在碱性条件下制备间三氟甲基苯丙醛二聚体,通过高分辨质谱、氢谱进行结构确证,以气相色谱法对盐酸西那卡塞原料药和制剂中该杂质进行检测。结果与结论合成并确证了盐酸西那卡塞中潜在基因毒性杂质间三氟甲基苯丙醛二聚体,采用自行建立并验证的气相色谱法对盐酸西那卡塞原料药和制剂进行了该杂质的检测,结果表明原料药中未检出,制剂中有检出,但低于标准限度15×10^(-6),安全风险可控。

3-(Trifluoromethyl)benzenepropanal dimer,which is a potentially genotoxic substance in cinacalcet hydrochloride,was synthesized with 3-(trifluoromethyl)benzenepropanal as the starting material.The structure of the target compound was identified by HR-MS,^(1)H-NMR and^(13)C-NMR.The content detection was established by gas chromatographic method and the results showed that it was not detected in the cinacalcet hydrochloride,but in the cinacalcet hydrochloride tablets.The impurity content was lower than the standard limit of 15×10^(-6),so the safety risk was controllable in the cinacalcet hydrochloride tablets.