An effective LC–MS/MS method was developed for the quantification of traces of 4-phenoxyphenyl-boronic acid, a potential genotoxic impurity, in ibrutinib drug. AtlantisT3 Column of dimensions: 150 × 4.6 mm (length x diameter) and particle size: 5.0 μm was used. Gradient elution using ammonium formate buffer (10 mM) and acetonitrile as mobile phase A and B, respectively, was employed. Mass detection was conducted in negative mode with selected ion monitoring (SIM) at m/z 231.02 for 4-phenoxyphenyl-boronic acid. The detection and quantitation limits were established for the said impurity and were found to be 0.134 µg/mL and 0.45 µg/mL, respectively. The developed LC–MS/MS method was validated as per ICH guidelines. The results of validation proved that the developed method was precise, accurate, linear, specific and robust. The method can be effectively used for routine quantification of 4-phenoxyphenyl-boronic acid impurity at trace levels in ibrutinib drug substance.

已开发出一种有效的LC-MS / MS方法，用于对依鲁替尼药物中痕量的4-苯氧基苯基硼酸（一种潜在的遗传毒性杂质）进行定量。AtlantisT3色谱柱的尺寸为：150×4.6 mm（长x直径），粒径：5.0μm。分别使用甲酸铵缓冲液（10 mM）和乙腈作为流动相A和B进行梯度洗脱。质谱检测是通过负离子模式进行的，其中选定的离子监测（SIM）在4-z氧基苯硼酸的m / z为231.02。确定了上述杂质的检测限和定量限，分别为0.134 µg / mL和0.45 µg / mL。根据ICH指南验证了开发的LC-MS / MS方法。验证结果表明，所开发的方法准确，准确，线性，特异性强。