Why should the pharmaceutical industry claim for the implementation of second-order chemometric models-A critical review

Abstract

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.

Keywords: Drug determination; Higher-order models; Pharmaceutical analysis; Quality by design (QbD); Second-order advantage.