Development and Validation of 1H Nuclear Magnetic Resonance Quantitative Method for Efavirenz API Quality Control

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-15 DOI:10.2174/0115734110307860240503080554

Eduardo Gomes Rodrigues de Sousa, Karina Rocha de Souza, Rosane Aguiar da Silva San Gil, Thiago Frances Guimaraes, Renata Ribeiro de Castro, Leonardo Lucchetti, Erika Martins de Carvalho

{"title":"Development and Validation of 1H Nuclear Magnetic Resonance Quantitative Method for Efavirenz API Quality Control","authors":"Eduardo Gomes Rodrigues de Sousa, Karina Rocha de Souza, Rosane Aguiar da Silva San Gil, Thiago Frances Guimaraes, Renata Ribeiro de Castro, Leonardo Lucchetti, Erika Martins de Carvalho","doi":"10.2174/0115734110307860240503080554","DOIUrl":null,"url":null,"abstract":"\n\nThe pharmaceutical industry is constantly looking for a better way to ensure\nand improve its products' safety, quality, and effectiveness. Since there are many attributes of the\ndrug substance and excipients that could potentially affect the Critical Quality Attributes (CQAs) of\nthe intermediates and the final product, the evaluation of the raw material's physicochemical characteristics\nis crucial as they directly affect the quality, safety, efficacy, and lot-to-lot consistency. Scientists\nrely on methods, like HPLC, HPTLC, LC-MS, GC-MS, and NMR, to analyze these substances.\nThe advantage of NMR is that it is considered a primary analytical method compared to other\nanalytical techniques.\n\n\n\nThis work aimed to present a simple, rapid, specific, and accurate method by proton Nuclear\nMagnetic Resonance spectroscopy (1H-NMR) developed to determine the activity of the antiretroviral\nEfavirenz’s (EFZ) Active Pharmaceutical Ingredient (API). The method was based on\nquantitative NMR spectroscopy (qNMR).\n\n\n\nA Bruker Avance spectrometer (11.7 Tesla, 500 MHz for 1H) with a 5mm probe was used.\nThe 1H-NMR signal at 7.54 ppm corresponding to the analyte of interest was employed to quantify\nthe drug. The method was validated for specificity, selectivity, intermediate precision, linearity,\nrange of work, accuracy, and robustness.\n\n\n\nThe method developed was specific and linear (r2 = 0.9998) with a value between 4.30\nmg/mL and 12.40 mg/mL. The relative standard deviation for accuracy and precision was 0.4% or\nless. The method's robustness was demonstrated by changing four different parameters, and the difference\namong each was 1.2% or less. The results of this work have been found to be in agreement\nwith those obtained from High-performance Liquid Chromatography (HPLC) analysis.\n\n\n\nThe method developed was specific and linear (r2 = 0.9998) between 4.30 mg/mL and 12.40 mg/mL. The relative standard deviation for accuracy and precision was 0.4% or less. The method's robustness was demonstrated by changing four different parameters; the difference among each was 1.2% or less. The results in this work agreed with those obtained from high-performance liquid chromatography analysis (HPLC).\n\n\n\nThe proposed method has been found to be a valuable and practical tool for quality\ncontrol. Its applicability to determining many APIs and saving solvent use and time is highlighted.\n","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.2174/0115734110307860240503080554","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

The pharmaceutical industry is constantly looking for a better way to ensure and improve its products' safety, quality, and effectiveness. Since there are many attributes of the drug substance and excipients that could potentially affect the Critical Quality Attributes (CQAs) of the intermediates and the final product, the evaluation of the raw material's physicochemical characteristics is crucial as they directly affect the quality, safety, efficacy, and lot-to-lot consistency. Scientists rely on methods, like HPLC, HPTLC, LC-MS, GC-MS, and NMR, to analyze these substances. The advantage of NMR is that it is considered a primary analytical method compared to other analytical techniques. This work aimed to present a simple, rapid, specific, and accurate method by proton Nuclear Magnetic Resonance spectroscopy (1H-NMR) developed to determine the activity of the antiretroviral Efavirenz’s (EFZ) Active Pharmaceutical Ingredient (API). The method was based on quantitative NMR spectroscopy (qNMR). A Bruker Avance spectrometer (11.7 Tesla, 500 MHz for 1H) with a 5mm probe was used. The 1H-NMR signal at 7.54 ppm corresponding to the analyte of interest was employed to quantify the drug. The method was validated for specificity, selectivity, intermediate precision, linearity, range of work, accuracy, and robustness. The method developed was specific and linear (r2 = 0.9998) with a value between 4.30 mg/mL and 12.40 mg/mL. The relative standard deviation for accuracy and precision was 0.4% or less. The method's robustness was demonstrated by changing four different parameters, and the difference among each was 1.2% or less. The results of this work have been found to be in agreement with those obtained from High-performance Liquid Chromatography (HPLC) analysis. The method developed was specific and linear (r2 = 0.9998) between 4.30 mg/mL and 12.40 mg/mL. The relative standard deviation for accuracy and precision was 0.4% or less. The method's robustness was demonstrated by changing four different parameters; the difference among each was 1.2% or less. The results in this work agreed with those obtained from high-performance liquid chromatography analysis (HPLC). The proposed method has been found to be a valuable and practical tool for quality control. Its applicability to determining many APIs and saving solvent use and time is highlighted.

查看原文本刊更多论文

用于依非韦伦原料药质量控制的 1H 核磁共振定量方法的开发与验证

制药业一直在寻找更好的方法来确保和提高产品的安全性、质量和有效性。由于药物和辅料的许多属性都可能影响中间体和最终产品的关键质量属性 (CQA)，因此对原材料理化特性的评估至关重要，因为它们直接影响到产品的质量、安全性、有效性和批次间的一致性。本研究旨在介绍一种简单、快速、特异和准确的质子核磁共振光谱法（1H-NMR），用于测定抗逆转录病毒药物依非韦伦（EFZ）活性药物成分（API）的活性。该方法以定量核磁共振光谱（qNMR）为基础，使用配有 5 毫米探针的布鲁克 Avance 光谱仪（11.7 特斯拉，1H 为 500 兆赫），利用 7.54 ppm 处与相关分析物相对应的 1H-NMR 信号对药物进行定量。对该方法的特异性、选择性、中间精密度、线性、工作范围、准确度和稳健性进行了验证。所建立的方法具有特异性和线性（r2 = 0.9998），线性范围为 4.30mg/mL 至 12.40 mg/mL。准确度和精密度的相对标准偏差不超过 0.4%。通过改变 4 个不同的参数证明了该方法的稳健性，每个参数之间的差异不超过 1.2%。所建立的方法在 4.30 mg/mL 至 12.40 mg/mL 之间具有特异性和线性（r2 = 0.9998）。准确度和精密度的相对标准偏差不超过 0.4%。通过改变四个不同的参数，证明了该方法的稳健性；每个参数之间的差异不超过 1.2%。该方法是一种有价值的质量控制实用工具。该方法适用于多种原料药的测定，节省了溶剂的使用和时间。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.