复方卡托普利片中未知杂质的来源与结构分析

Identification of the Unknown Impurity in Compound Captopril Tablet and Its Source Analysis

关键词:  复方卡托普利片  未知杂质  液质联用

Key words:  Compound Captopril tablet  unknown impurity  LC-MS

摘要:

目的 对复方卡托普利片中新发现的未知杂质进行来源分析和结构的初步确认，以期为该制剂改进工艺和提高标准提供依据。方法 采用Kromasil苯基色谱柱（250 mm×4.6 mm，5 μm），以水-磷酸（550︰0.5）和甲醇为流动相进行梯度洗脱，检测波长为210 nm。对市售的复方卡托普利片中的该未知杂质的含量进行系统的评价；同时采用液质联用的方法对该未知杂质的结构进行确认。结果 该未知杂质为复方制剂的2种原料卡托普利和氢氯噻嗪在受热过程中产生的二聚物，分子式为C₁₆H₂₃N₄O₇S₃Cl；市售产品多数含有该杂质。结论 本研究为复方卡托普利片的质量控制和工艺优化提供了参考依据。

Abstract:

OBJECTIVE To improve the quality and provide technological support for reducing the impurity content of Compound Captopril tablet, the source and structure determination of the unknown-impurity is studied. METHODS A Kromasil Phenyl column (250 mm×4.6 mm, 5 μm) was used. The wavelength of UV detector was 210 nm. HPLC gradient elution was used with water-phosphoric acid (550︰0.5) and methanol as mobile phase to find the source and determine the content of the unknown impurity in Compound Captopril tablets. The structure of the unknown impurity was identified by LC-MS. RESULTS The unknown impurity was elucidated as C₁₆H₂₃N₄O₇S₃Cl, which was the dipolymer of hydrochlorothiazide and captopril by heating, and was included in most of the domestic generic Compound Captopril tablet. CONCLUSION This study provides reference for the improvement of quality control and process optimization of Compound Captopril tablet.