高效液相色谱法测定盐酸氨溴索口服溶液的有关物质

HPLC determination of related substances in Ambroxol hydrochloride oral solution

目的采用高效液相色谱法测定盐酸氨溴索口服溶液中杂质B[反式-4-（6,8-二溴-四氢喹唑啉环己醇）盐酸盐]与杂质E（2-氨基-3,5-二溴苯甲醛）的含量。方法色谱柱为Ultimate XB-C18（250 mm×4.6mm,5μm）,以0.01 mol·L^-1磷酸氢二铵（用磷酸调节pH至7.0）-乙腈（50：50）为流动相,检测波长为250 nm（检测杂质B）与238 nm（检测杂质E）,柱温为40℃,流速为1 mL·min^-1,进样量为20μL。结果杂质B进样浓度在1.215-19.44μg·mL^-1与峰面积呈良好的线性关系（r=0.999 9）,检测限为2.43 ng,平均回收率均在100.0%-100.6%（n=3）,RSD均〈1.6%;杂质E进样浓度在1.032-16.512μg·mL^-1与峰面积呈良好的线性关系（r=0.999 4）,检测限为0.825 ng;平均回收率均在95.9%-100.1%（n=3）,RSD均〈0.65%。结论该方法简单可行、灵敏度高,适用于盐酸氨溴索口服液中有关物质的质量控制。

Objective To establish an HPLC method to determine the content of impurity B [trans-4-（6, 8-dibromo-1, 4-dihydroquinazolin-3（2H）-yl） cyclohexanol hydrochloride] and impurity E（2-amino-3, 5-dibromobenzaldehyde） in Ambroxol hydrochlorid oral solution. Methods Ultimate XB-C18 column was used with the mobile phase composed of acetonitrile-0.01 mol·L^- 1 ammonium hydrogen phosphate（50 ：50）. The detection wavelength was 250 nm for impurity B and 238 nm for impurity E. The column temperature was 40 ℃, and the flow rate was 1.0 mL·min^- 1, the sample size was 20 μL. Results The calibration curve of impurity B and impurity E had good linearity at 1.215-19.44 μg·mL^- 1（r = 0.999 9） and 1.032- 16.512 μg·mL^- 1（r = 0.999 4）, the minimum detection limit of impurity B and impurity E were 2.43 ng and 0.825 ng. The average recoveries of impurity B and impurity E was at 100.0%- 100.6%（RSD 〈1.6%） and 95.9%- 100.1%（RSD〈 0.65%）. Conclusion The method is simple and highly sensitive and suitable for the quality control of related substances in Ambroxol hydrochloride oral solution.