| 高效液相色谱-质谱联用分析磷酸可待因及其精氨酸布洛芬复方中的有关物质 |
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| 引用本文： | Soumia Cheddah,;杭太俊.高效液相色谱-质谱联用分析磷酸可待因及其精氨酸布洛芬复方中的有关物质[J].中国药学,2014,23(10):694-710. |
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| 作者姓名： | Soumia Cheddah ;杭太俊 |
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| 作者单位： | [1]中国药科大学药物分析教研室,江苏南京210009; [2]中国药科大学药物质量控制及药物警成重点实验室,江苏南京210009 |
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| 基金项目： | Foundation items： National Key Technology R＆D Program ＂New Drug Innovation＂ of China （Grant No. 2009ZX09301 ）.; The authors thank the Pharmaceutics Department of China Pharmaceutical University for providing the drug product and are grateful to the Pharmaceutical Chemistry Department for their help with the synthesis of codeine-ibuprofen ester. Conceptual and technical supports from colleagues especially Fangxian Shao are appreciated. The project was financially supported by the National Key Technology R＆D Program ＂New Drug Innovation＂ of China （Grant No. 2009ZX09301）. |
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| 摘 要： | 建立了高效液相色谱法检查磷酸可待因、磷酸可待因与精氨酸布洛芬复方的有关物质，并采用HPLC-TOF／MS和LC—MS／MS对磷酸可待因及两种复方药物产生的降解产物进行了结构鉴定。色谱柱为ClR（250mm×4．6mm，5μm），柱温50℃，流速1mL／min，检测波长245nm，醋酸铵（0．04M，用醋酸调pH6．0）-乙腈（92：8，v／v）为流动相A，乙腈为流动相B，梯度洗脱。磷酸可待因在氧化条件下很不稳定产生了两个N-氧可待因异构体，在碱性破坏中得到了新的杂质，其结构可能为6-羟基-3-甲氧基-17-甲基-7，8-双脱氢吗啡-5-醇。在酸性破坏条件下磷酸可待因和精氨酸布洛芬可发生酯化反应。所建立的HPLC方法灵敏、准确，可有效测定磷酸可待因、磷酸可待因与精氨酸布洛芬复方的有关物质，并对产生的降解产物进行了结构鉴定，为更好的控制磷酸可待因与磷酸可待因复方药物的质量提供了依据。
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| 关 键 词： | 磷酸可待因 降解产物 可待因-布洛芬酯 反应杂质 Lc-MS |
| 收稿时间： | 2014-03-23 |
Separation and characterization of degradation/interaction products of codeine phosphate in ibuprofen arginate/codeine phosphate combination formulation by HPLC coupled with MS analysis |
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| Soumia Cheddah,Taijun Hang.Separation and characterization of degradation/interaction products of codeine phosphate in ibuprofen arginate/codeine phosphate combination formulation by HPLC coupled with MS analysis[J].Journal of Chinese Pharmaceutical Sciences,2014,23(10):694-710. |
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| Authors: | Soumia Cheddah Taijun Hang |
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| Affiliation: | Soumia Cheddah, Taijun Hang( 1. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China 2. Key Laboratory of Drug Quality Control and Pharmaeovigilance, China Pharmaceutical University, Nanjing 210009, China) |
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| Abstract: | A simple HPLC method was developed and validated according to the ICH guidelines to detect and quantify the related substances of codeine phosphate in the raw material and in its combination formulation with ibuprofen before and after forced degradation. These products were further identified by using HPLC-TOF/MS and MS/MS techniques. Good separations were obtained on a C18 （250 min×4.6 mm, 5 μm） column maintained at 50 ℃ with linear gradient elution by a mixture of mobile phase A （ammonium acetate （pH 6.0 regulated with acetic acid, 0.04 M）-acetonitrile （92：8, v/v）） and mobile phase B （acetonitrile） at a flow rate of 1 mL/min. UV detection was set at 245 nm. Codeine was found to be instable under oxidation with the production of mainly two stereoisomers of codeine N-oxide. A new degradation product, not reported previously, was detected under alkaline hydrolysis, which was identified as 6-hydroxy-3-methoxy-17-methyl-7,8-didehydromorphinan-5-ol and shortly named as deshydrolevomethorphandiol. The esterification of codeine by ibuprofen occurred in very small amount and only under acidic stress. These results contribute to the understanding of the degradation behavior of codeine and its interaction with ibuprofen. The developed method is sensitive and precise and could be applied for the quality control of codeine bulk drug, preparations of codeine phosphate, and its combination with ibuprofen. |
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| Keywords: | Codeine phosphate Degradation product Codeine-ibuprofen ester Interaction impurity LC-MS |
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