Bandaru Lova Gani Raju, Konduru Naresh, Kowtharapu Leela Prasad, Regulagadda Suryanarayana, Kanuparthy Phani Raja, Gundla Rambabu
Department of Chemistry, School of Science, GITAM (Deemed to be University) Hyderabad, Sangareddy, Telangana, India.
Analytical Research and Development, Zhuhai Resproly Pharmaceutical Technology Co. Ltd, Zhuhai city, Guangdong province, China.
Biomed Chromatogr. 2023 Apr;37(4):e5576. doi: 10.1002/bmc.5576. Epub 2023 Jan 26.
A related-substances method was developed for the anticancer drug formulation apalutamide 60 mg tablets and validated using a liquid chromatography gradient elution method. All of the impurities and degradants were separated using the Luna Omega 5 μm Polar C , (250 × 4.6) mm HPLC column with a 1.0 ml min flow rate. The detection was done at 225 nm by injecting the 10 μl of injection volume, controlling the sample temperature at 10°C and maintaining the column compartment temperature at 30°C. The total run time was 85 min. A 0.01 m disodium phosphate dihydrate pH 4.20 ± 0.05 buffer mixed with acetonitrile in the ratio of 73:27 (v/v) was used as mobile phase A. Mobile phase B consisted of water and acetonitrile in the ratio 30:70 (v/v). The proposed method was validated as per the current regulatory guidelines. The method precisions (RSD) at 100% specification level were 1.41, 1.74, 1.84, and 1.66% for the four impurities. The accuracy results were obtained between 96.0 and 106.3% for the limit of quantitation to the 150% level. The standard and sample solutions stability were established for 44 h at 10°C. The correlation coefficient (r) value was >0.999 for all four impurities, indicating good linearity between the concentration and peak response: 0.9999, 0.9999, 0.9999 and 1.0000. These results show the method's linearity. The three filter compatibility was proved and it was concluded that 0.45 μm Nylon, PTFE and PVDF filters are suitable. The robustness of the method was established by varying the conditions. The method specificity was proved and the forced degradation data reveal the method's stability-indicating nature.
开发了一种用于抗癌药物阿帕他胺60毫克片剂的有关物质方法，并采用液相色谱梯度洗脱法进行验证。使用Luna Omega 5μm Polar C，(250×4.6)mm高效液相色谱柱，流速为1.0ml/min，分离所有杂质和降解产物。进样体积为10μl，在225nm处进行检测，将样品温度控制在10°C，柱温箱温度保持在30°C。总运行时间为85分钟。以0.01m磷酸二氢二钠pH 4.20±0.05缓冲液与乙腈按73:27(v/v)的比例混合作为流动相A。流动相B由水和乙腈按30:70(v/v)的比例组成。所提出的方法根据现行监管指南进行了验证。四种杂质在100%规格水平下的方法精密度（相对标准偏差）分别为1.41%、1.74%、1.84%和1.66%。定量限至150%水平时的准确度结果在96.0%至106.3%之间。标准溶液和样品溶液在10°C下的稳定性确定为44小时。四种杂质的相关系数（r）值均>0.999，表明浓度与峰响应之间具有良好的线性关系：0.9999、0.9999、0.9999和1.0000。这些结果表明了该方法的线性。证明了三种滤膜的兼容性，得出0.45μm尼龙、聚四氟乙烯和聚偏氟乙烯滤膜适用的结论。通过改变条件确定了该方法的稳健性。证明了该方法的专属性，强制降解数据显示了该方法的稳定性指示特性。
