Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario and Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina.
Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario and Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina.
J Pharm Biomed Anal. 2020 Feb 5;179:112965. doi: 10.1016/j.jpba.2019.112965. Epub 2019 Nov 4.
Today, pharmaceutical products are submitted to a large number of analytical tests, planned to either ensure or construct their quality. The official methods of analysis used to perform these determinations are very different in nature, but almost all demand the intensive use of reagents and manpower as major drawbacks. Thus, analytical development is continuously evolving to find fast and smart approaches. First-order chemometric models are well-known in the pharmaceutical industry, and are extensively used in many fields. Such is the impact of chemometric models that regulatory agencies include them in guidelines and compendia. However, the mention or practical application of higher-order models in the pharmaceutical industry is rather scarce. Herein, we try to bring a brief introduction to chemometric models and useful literature references, focusing on higher-order chemometric models (HOCM) applied to reduce manpower, reagent consumption, and time of analysis, without sacrificing accuracy or precision, while gaining selectivity and sensitivity. The advantages and drawbacks of HOCM are also discussed, and the comparison to first-order chemometric models is also analyzed. Along the work, HOCM are evidenced as a powerful tool for the pharmaceutical industry; moreover, its implementation is shown during several steps of production, such as identification, purity test and assay, and other applications as homogeneity of API distribution, Process Analytical Technology (PAT), Quality by Design (QbD) or natural product fingerprinting. Among these topics, qualitative and quantitative applications were covered. Experimental approaches of chemometrics coupled to several analytical techniques such as UV-vis, fluorescence and vibrational spectroscopies (NIR, MIR and Raman), and other techniques as hyphenated-chromatography and electrochemical techniques applied to production and analysis are discussed throughout this work.
如今，药品需要进行大量的分析测试，以确保或构建其质量。用于执行这些测定的官方分析方法在性质上有很大的不同，但几乎都需要大量使用试剂和人力，这是主要的缺点。因此，分析方法的开发一直在不断发展，以寻求快速和智能的方法。一阶化学计量学模型在制药行业中是众所周知的，并且在许多领域得到了广泛的应用。化学计量学模型的影响如此之大，以至于监管机构将其纳入了指南和药典中。然而，在制药行业中，高阶模型的提及或实际应用却相当罕见。在此，我们尝试简要介绍化学计量学模型和有用的文献参考，重点介绍应用于减少人力、试剂消耗和分析时间而不牺牲准确性或精密度的高阶化学计量学模型（HOCM），同时提高选择性和灵敏度。还讨论了 HOCM 的优缺点，并对一阶化学计量学模型进行了分析比较。在整个工作过程中，HOCM 被证明是制药行业的有力工具；此外，还展示了其在生产的多个步骤中的实施情况，如鉴别、纯度测试和含量测定，以及其他应用，如 API 分布均匀性、过程分析技术（PAT）、质量源于设计（QbD）或天然产物指纹图谱。在这些主题中，涵盖了定性和定量应用。本文讨论了化学计量学与多种分析技术（如紫外-可见、荧光和振动光谱（近红外、中红外和拉曼））相结合的实验方法，以及其他技术，如联用色谱和电化学技术在生产和分析中的应用。
