目的: 建立高效液相色谱法检测奥拉帕利原料中的有关物质。方法: 采用YMC-Pack pro C18 AS(150 mm×4.6 mm,3 μm)色谱柱,以0.05 mol·L-1的磷酸二氢钾(用稀磷酸调pH至3.0)-甲醇-乙腈(90∶5∶5)为流动相A,甲醇-乙腈-水(45∶45∶10)为流动相B,进行梯度洗脱,流速0.8 mL·min-1,柱温30 ℃,检测波长210 nm,进样量10 μL。结果: 空白溶剂不干扰供试品溶液有关物质测定,系统适用性溶液中已知杂质Ⅰ~Ⅶ及未知杂质在该色谱系统中分离完好;奥拉帕利质量浓度在0.033~411.623 μg·mL-1,杂质Ⅰ~Ⅶ质量浓度均在0.05~3.0 μg·mL-1与其峰面积呈较好的线性关系,其r均在0.999以上;杂质Ⅰ~Ⅶ平均回收率均大于92.0%(RSD均小于4.0%)。结论: HPLC法检查奥拉帕利原料有关物质方法专属性强,灵敏度高,准确度高,精密度好,可满足奥拉帕利原料有关物质检测需求。
Objective: To establish an HPLC method for the determination of related substances in olaparib raw materials. Methods: By using YMC-Pack pro C18 AS(150 mm×4.6 mm, 3 μm) column, 0.05 mol·L-1 potassium dihydrogen phosphate (pH 3.0 adjusted with dilute phosphoric acid)-methanol-acetonitrile (90∶5∶5) was as mobile phase A and methanol-acetonitrile-water (45∶45∶10) was as mobile phase B, in gradient elution, with flow rate of 0.8 mL·min-1. The column temperature was 30 ℃, the detection wavelength was 210 nm, and the injection volume was 10 μL. Results: The solvent blank did not interfere with the determination of relevant substances in the test solution, the known impurities Ⅰ-Ⅶ and unknown impurities in the system suitability solution were well separated in the chromatographic system. Olaparib had a good linear relationship with its peak area in the concentration range of 0.083-333.133 μg·mL-1. The concentrations of impurities Ⅰ-Ⅶ were 0.05-3.0 μg·mL-1, there were good linear relationships with their peak area, and their r were 0.999 7 or above. The average recoveries of impurities Ⅰ-Ⅶ were all above 92.0%, and RSDs were less than 4.0%. Conclusion: The HPLC method for the detection of the related substances of olaparib raw materials has strong specificity, high sensitivity, high accuracy and good precision, which can meet the requirements for the detection of related substances of olaparib raw materials.
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