依托红霉素片有关物质分析

目的：研究依托红霉素片中的有关物质分布情况。方法：收集14个厂家130批依托红霉素片样品，建立HPLC方法考察有关物质，对主要组分进行定性定量；色谱条件：采用CAPCELLPAK-MGⅡ C₁₈ （4.6 mm×250 mm，5 μm）色谱柱，以0.05 mol·L^-1磷酸氢二钾（用20%磷酸调节pH至8.2）-乙腈（40∶60）为流动相，检测波长205 nm。未知组分经制备后，采用质谱技术对结构进行初步鉴定；质谱条件：质谱离子源为ESI，模式为负离子扫描，碰撞能量10~30 eV，毛细管电压4.5 kV。通过破坏实验确定有关物质产生的途径，分析样品中有关物质的主要来源。结果：依托红霉素片除主成分峰外，还检测出20个有关物质，其中已知有关物质有7个，分别为N-去甲基红霉素A、红霉素C、红霉素A、脱水红霉素A、表红霉素A烯醇醚、红霉素B、红霉素A烯醇醚；未知的主要有关物质结构推断为红霉素A丙酸酯烯醇醚。制剂中2个主要已知有关物质（红霉素A、脱水红霉素A）含量与原料来源密切相关。结论：依托红霉素片稳定性较好，其有关物质的控制应从原料着手，以保证制剂的质量。

Objective: To study the distribution of related substances in erythromycin estolate tablets.Methods: Erythromycin estolate tablets with 130 batches were collected from 14 manufacturers.An HPLC method was established to determine the related substances in erythromycin estolate tablets and to locate the main components.Chromatographic conditions:CAPCELLPAK-MGⅡ C₁₈column(4.6 mm×250 mm,5 μm) was used with isocratic elution of a mobile phase consisting of 0.05 mol·L^-1 dipotassium hydrogen phosphate solution (adjusted to pH 8.2 with 20% phosphoric acid) -acetonitrile(40:60).The UV detection wavelength was 205 nm.MS analysis technique was used to identify the structure of the unknown components after collection.MSD parameters:Data were collected in negative ion modes with ESI as the ion resource,collision energy 10-30 eV,and capillary voltage 4.5 kV.The producing pathways of the related substances were proposed with stress destruction experiments and the main sources of the related substances in the sample were analyzed.Results: 20 related substances were detected,including 7 known substances (N-demethyl erythromycin A,erythromycin C,erythromycin A,dehydrated erythromycin A,erythromycin A enol ether,erythromycin B,erythromycin A enol ether).The main unknown related substance was inferred to be erythromycin A propionate enol ether.The source of 2 known related substances(erythromycin A and dehydrated erythromycin A) was closely related to the bulk sample.Conclusion: Erythromycin estolate tablets are relative stable.Contents of various related substances should be controlled in bulk manufacturing process to ensure the quality of preparations.