Maggio Rubén M, Calvo Natalia L, Vignaduzzo Silvana E, Kaufman Teodoro S
Instituto de Química Rosario (IQUIR, CONICET-UNR) and Área Análisis de Medicamentos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario S2002LRK, Argentina.
Instituto de Química Rosario (IQUIR, CONICET-UNR) and Área Análisis de Medicamentos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario S2002LRK, Argentina.
J Pharm Biomed Anal. 2014 Dec;101:102-22. doi: 10.1016/j.jpba.2014.04.016. Epub 2014 Apr 24.
Current standards and regulations demand the pharmaceutical industry not only to produce highly pure drug substances, but to achieve a thorough understanding of the impurities accompanying their manufactured drug substances and products. These challenges have become important goals of process chemistry and have steadily stimulated the search of impurities after accelerated or forced degradation procedures. As a result, impurity profiling is one of the most attractive, active and relevant fields of modern pharmaceutical analysis. This activity includes the identification, structural elucidation and quantitative determination of impurities and degradation products in bulk drugs and their pharmaceutical formulations. Nuclear magnetic resonance (NMR) spectroscopy has evolved into an irreplaceable approach for pharmaceutical quality assessment, currently playing a critical role in unequivocal structure identification as well as structural confirmation (qualitative detection), enabling the understanding of the underlying mechanisms of the formation of process and/or degradation impurities. NMR is able to provide qualitative information without the need of standards of the unknown compounds and multiple components can be quantified in a complex sample without previous separation. When coupled to separative techniques, the resulting hyphenated methodologies enhance the analytical power of this spectroscopy to previously unknown levels. As a result, and by enabling the implementation of rational decisions regarding the identity and level of impurities, NMR contributes to the goal of making better and safer medicines. Herein are discussed the applications of NMR spectroscopy and its hyphenated derivate techniques to the study of a wide range pharmaceutical impurities. Details on the advantages and disadvantages of the methodology and well as specific challenges with regards to the different analytical problems are also presented.
当前的标准和法规要求制药行业不仅要生产高纯度的原料药，还要全面了解其生产的原料药和产品中伴随的杂质。这些挑战已成为工艺化学的重要目标，并不断激发人们在加速或强制降解程序后寻找杂质。因此，杂质剖析是现代药物分析中最具吸引力、最活跃且最相关的领域之一。这项工作包括对原料药及其药物制剂中的杂质和降解产物进行鉴定、结构解析和定量测定。核磁共振（NMR）光谱已发展成为药物质量评估中一种不可替代的方法，目前在明确的结构鉴定以及结构确认（定性检测）中发挥着关键作用，有助于理解工艺和/或降解杂质形成的潜在机制。NMR能够在无需未知化合物标准品的情况下提供定性信息，并且可以在不进行预先分离的情况下对复杂样品中的多种成分进行定量。当与分离技术结合使用时，由此产生的联用方法将这种光谱的分析能力提升到了前所未有的水平。因此，通过能够就杂质的身份和水平做出合理决策，NMR有助于实现生产出更好、更安全药物的目标。本文讨论了NMR光谱及其联用衍生技术在广泛的药物杂质研究中的应用。还介绍了该方法的优缺点以及针对不同分析问题的具体挑战的详细信息。
