{"title":"基于国家药品抽检的酮康唑乳膏中有关物质的定性和定量评价","authors":"Changying Xin, Yanbin Xun, Yi Zhou, Fei Wang, Feng Li, Qiong Wu, Panpan Wu, Demin Ding, Liqun Liu, Longshan Zhao, Lihong Yang","doi":"10.1186/s13065-025-01629-5","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Establishing an analytical method for the detection of related substances in ketoconazole cream is essential for improving product quality standards and ensuring the safety of this formulation.</p><h3>Methods</h3><p>In the 2024 National Drug Sampling Specification, we developed a novel high-sensitivity high-performance liquid chromatography (HPLC) method that effectively separates six known impurities, four preservatives, and one antioxidant present in ketoconazole creams. These creams were sourced from random market sampling and exhibited variations in prescription composition across 14 different manufacturers. Subsequently, we conducted the extraction, isolation, and characterization of common unknown impurities from these creams using mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and infrared (IR) techniques. Furthermore, the structural analysis of unknown impurities within a specific enterprise was performed using high-resolution mass spectrometry and specialized software.</p><h3>Results</h3><p>The established method has been thoroughly validated, demonstrating its specificity, accuracy, sensitivity, and excellent repeatability, thereby confirming its suitability for determining related substances in ketoconazole creams from various manufacturers. This method allowed for both quantitative and qualitative evaluations of impurity content across different manufacturers, identifying sulfonated impurities in ketoconazole creams for the first time and analyzing their formation mechanisms. Furthermore, strategies to reduce these impurities were proposed through correlation analysis and process validation. Additionally, this study innovatively introduced a solvent smoothing agent to mitigate solvent effects, thereby preventing the degradation of the active pharmaceutical ingredient (API) during the heating and dissolution process of the cream matrix. This technique is applicable to the pretreatment of various cream-related substance determinations.</p><h3>Conclusions</h3><p>This method provides substantial reference value for establishing analytical methods for related substances in Ketoconazole cream and offers technical support for regulatory agencies in evaluating the quality of Ketoconazole cream.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01629-5","citationCount":"0","resultStr":"{\"title\":\"Qualitative and quantitative assessment of related substances for ketoconazole cream based on national drug sampling inspection in China\",\"authors\":\"Changying Xin, Yanbin Xun, Yi Zhou, Fei Wang, Feng Li, Qiong Wu, Panpan Wu, Demin Ding, Liqun Liu, Longshan Zhao, Lihong Yang\",\"doi\":\"10.1186/s13065-025-01629-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Establishing an analytical method for the detection of related substances in ketoconazole cream is essential for improving product quality standards and ensuring the safety of this formulation.</p><h3>Methods</h3><p>In the 2024 National Drug Sampling Specification, we developed a novel high-sensitivity high-performance liquid chromatography (HPLC) method that effectively separates six known impurities, four preservatives, and one antioxidant present in ketoconazole creams. These creams were sourced from random market sampling and exhibited variations in prescription composition across 14 different manufacturers. Subsequently, we conducted the extraction, isolation, and characterization of common unknown impurities from these creams using mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and infrared (IR) techniques. Furthermore, the structural analysis of unknown impurities within a specific enterprise was performed using high-resolution mass spectrometry and specialized software.</p><h3>Results</h3><p>The established method has been thoroughly validated, demonstrating its specificity, accuracy, sensitivity, and excellent repeatability, thereby confirming its suitability for determining related substances in ketoconazole creams from various manufacturers. This method allowed for both quantitative and qualitative evaluations of impurity content across different manufacturers, identifying sulfonated impurities in ketoconazole creams for the first time and analyzing their formation mechanisms. Furthermore, strategies to reduce these impurities were proposed through correlation analysis and process validation. Additionally, this study innovatively introduced a solvent smoothing agent to mitigate solvent effects, thereby preventing the degradation of the active pharmaceutical ingredient (API) during the heating and dissolution process of the cream matrix. This technique is applicable to the pretreatment of various cream-related substance determinations.</p><h3>Conclusions</h3><p>This method provides substantial reference value for establishing analytical methods for related substances in Ketoconazole cream and offers technical support for regulatory agencies in evaluating the quality of Ketoconazole cream.</p></div>\",\"PeriodicalId\":496,\"journal\":{\"name\":\"BMC Chemistry\",\"volume\":\"19 1\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01629-5\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s13065-025-01629-5\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1186/s13065-025-01629-5","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Qualitative and quantitative assessment of related substances for ketoconazole cream based on national drug sampling inspection in China
Background
Establishing an analytical method for the detection of related substances in ketoconazole cream is essential for improving product quality standards and ensuring the safety of this formulation.
Methods
In the 2024 National Drug Sampling Specification, we developed a novel high-sensitivity high-performance liquid chromatography (HPLC) method that effectively separates six known impurities, four preservatives, and one antioxidant present in ketoconazole creams. These creams were sourced from random market sampling and exhibited variations in prescription composition across 14 different manufacturers. Subsequently, we conducted the extraction, isolation, and characterization of common unknown impurities from these creams using mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and infrared (IR) techniques. Furthermore, the structural analysis of unknown impurities within a specific enterprise was performed using high-resolution mass spectrometry and specialized software.
Results
The established method has been thoroughly validated, demonstrating its specificity, accuracy, sensitivity, and excellent repeatability, thereby confirming its suitability for determining related substances in ketoconazole creams from various manufacturers. This method allowed for both quantitative and qualitative evaluations of impurity content across different manufacturers, identifying sulfonated impurities in ketoconazole creams for the first time and analyzing their formation mechanisms. Furthermore, strategies to reduce these impurities were proposed through correlation analysis and process validation. Additionally, this study innovatively introduced a solvent smoothing agent to mitigate solvent effects, thereby preventing the degradation of the active pharmaceutical ingredient (API) during the heating and dissolution process of the cream matrix. This technique is applicable to the pretreatment of various cream-related substance determinations.
Conclusions
This method provides substantial reference value for establishing analytical methods for related substances in Ketoconazole cream and offers technical support for regulatory agencies in evaluating the quality of Ketoconazole cream.
期刊介绍：
BMC Chemistry, formerly known as Chemistry Central Journal, is now part of the BMC series journals family.
Chemistry Central Journal has served the chemistry community as a trusted open access resource for more than 10 years – and we are delighted to announce the next step on its journey. In January 2019 the journal has been renamed BMC Chemistry and now strengthens the BMC series footprint in the physical sciences by publishing quality articles and by pushing the boundaries of open chemistry.
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