HPLC法测定盐酸妥洛特罗中的有关物质

Determination of the Related Substances in Tulobuterol Hydrochloride by HPLC

建立了HPLC法测定盐酸妥洛特罗(1)中的有关物质,即邻氯苯乙酮(2)、α-溴代邻氯苯乙酮(3)、2,2-溴代邻氯苯乙酮(4)、1-(2-氯苯基)乙醇(5)、2-氯苯基环氧乙烷(6)、1-(2-氯苯基)-1,2-乙二醇(7)、2,2-溴代邻氯苯乙醇(8)和1-叔丁胺基-1-(2-氯苯基)乙醇盐酸盐(9)。色谱柱采用Agilent Zorbax Eclipse Plus C_(18)柱(4.6 mm×250 mm,5μm),以辛烷磺酸钠缓冲液∶乙腈(90∶10)为流动相A,乙腈为流动相B,梯度洗脱。流速为1.0 ml/min,检测波长为215 nm,柱温为30℃。结果显示,1和杂质2~9均分离良好,且在各自浓度范围内线性关系良好;2~9的平均回收率(n=12)为100.3%~106.6%,RSD为2.6%~8.7%。1、2、3、5、6、7、9的检测限为0.05μg/ml,4和8的检测限为0.15μg/ml。建立的方法准确性好、灵敏度高,可用于1中有关物质的测定。

An HPLC method was established for the determination of related substances,namely 2'-chloroacetophenone(2),2-bromo-2'-chloroacetophenone(3),2,2-bromo-2'-chloroacetophenone(4),1-(2-chlorophenyl)ethanol(5),2-chlorophenyl ethylene oxide(6),1-(2-chlorophenyl)-1,2-glycol(7),2,2-bromo-2'-chlorophenethyl alcohol(8)and 1-tert-butylamino-1-(2-chlorophenyl)ethanol hydrochloride(9),in tulobuterol hydrochloride(1).The Agilent Zorbax Eclipse Plus C_(18) column(4.6 mm×250 mm,5μm)was used,and the analysis was carried out in the gradient elution mode,with sodium octane sulfonate buffer∶acetonitrile(90∶10)as mobile phase A,and acetonitrile as mobile phase B.The flow rate was 1.0 ml/min,the detection wavelength was 215 nm,and the column temperature was 30℃.The results showed that the peaks of 1 and impurities 2-9 were well separated,and it was linear for 1-9 in the corresponding concentration ranges.The average recoveries(n=12)of 2-9 were 100.3%-106.6%,with the RSDs of 2.6%-8.7%.The detection limit was 0.05μg/ml for 1,2,3,5,6,7 and 9,and 0.15μg/ml for 4 and 8.The established method has good accuracy and high sensitivity,which can be used for the determination of related substances in 1.