HPLC法测定N-叔丁氧羰基-5,7-二氯-1,2,3,4-四氢异喹啉-6-羧酸中的有关物质

Determination of Related Substances in N-tert-Butoxycarbonyl-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic Acid by HPLC

建立了HPLC法测定立他司特的关键起始物料N-叔丁氧羰基-5,7-二氯-1,2,3,4-四氢异喹啉-6-羧酸(1)中的有关物质。采用Thermo Acclaim~(TM) Mixed-Mode WAX-1柱(4.6 mm×250 mm,5μm),以30 mmol/L磷酸二氢钾溶液和乙腈(体积比95∶5)为流动相A,以乙腈和四氢呋喃(体积比80∶20)为流动相B,梯度洗脱。流速为0.9 mL/min,柱温为30℃,检测波长为205 nm,进样量为50μL。结果显示,主成分与各杂质间分离度良好,且在相应浓度范围内线性关系良好。平均回收率(n=9)为96.4%~105.6%,RSD均≤5.1%。该方法操作简单、准确、可靠,适用于1中有关物质的测定。

An HPLC method was established to determine the related substances in N-tert-butoxycarbonyl-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid(1),a key starting material for liftegrast.A Thermo Acclaim^(TM) Mixed-Mode WAX-1 column(4.6 mm×250 mm,5μm)was used,and the analysis was carried out in the gradient elution mode with 30 mmol/L potassium dihydrogen phosphate solution-acetonitrile(95:5)as mobile phase A,and acetonitrile-tetrahydrofuran(80:20)as mobile phase B.The flow rate was 0.9 mL/min,the column temperature was 30℃,the detection wavelength was 205 nm,and the injection amount was 50μL.The results showed that the separation between the main component and various impurities was good,and it was linear for the main component and various impurities in the corresponding concentration ranges.The average recoveries(n=9)were 96.4%-105.6%,with the RSDs less than 5.1%.This method is easy to operate,accurate,and reliable,which is suitable for the determination of related substances in1.