尼莫地平口服溶液中降解杂质的结构鉴定及分析

Structural Identification and Analysis of Degradation Impurities in Nimodipine Oral Solution

关键词:  尼莫地平  结构解析  降解杂质  高效液相色谱-质谱

Key words:  nimodipine  structural identification  degradation impurity  HPLC-MS

摘要:

目的 对尼莫地平口服溶液中2个未知降解杂质进行结构鉴定和分析测试。方法 通过二维液相色谱-高分辨质谱（2DLC-HRMS）推测未知杂质的化学结构，并采用定向合成的方式获得杂质单体，经核磁共振¹H-NMR、¹³C-NMR对杂质结构进行确证，采用Thermo Syncronis C₁₈（250 mm×4.6 mm，5 μm）色谱柱，以5 mmol·L^-1磷酸二氢钾（pH 2.8）为流动相A，以甲醇-乙腈（50∶50）为流动相B，梯度洗脱；流速为1.0 mL·min^-1；柱温为30℃；检测波长为235 nm。结果 尼莫地平与其降解杂质分离良好，各杂质校正因子均在0.80~1.10。结论 建立的方法专属性好，可有效分离和测定尼莫地平口服溶液中的有关物质。本研究可为尼莫地平口服溶液及其他剂型的杂质控制提供参考。

Abstract:

OBJECTIVE To identify and analyze two unknown degradation impurities in nimodipine oral solution. METHODS The chemical structure of the unknown impurity was deduced by two-dimensional liquid chromatography-high resolution mass spectrometry(2DLC-HRMS), and the impurity monomer was obtained by directional synthesis. The structure of the impurity was confirmed by ¹H-NMR and ¹³C-NMR, chromatographic separations were performed on an Thermo Syncronis C₁₈(250 mm×4.6 mm, 5 μm) column. Using 5 mmol·L^-1 potassium dihydrogen phosphate buffer(pH 2.8) as mobile phase A, while methanol-acetonitrile(50:50) was mobile phase B, with gradient elution. The mobile phase was pumped at 1.0 mL·min^-1. The column temperature was 30℃. The detection wavelength was 235 nm. RESULTS Nimodipine and its related substances had good separation. The correction factors of every impurities ranged from 0.80 to 1.10. CONCLUSION The established method has good specificity and can effectively isolate and determine the related substances in nimodipine oral solution. This study provides a reference to guide the impurity control of nimodipine oral solution and other dosage forms.