Fourier Transform Infrared Spectroscopy for Quantitative Determination of Drug Purity in Pharmaceutical Dosage Forms: Recent Advances, Validation Strategies, and Chemometric Applications.

The quantitative determination of drug purity is a critical aspect of pharmaceutical quality control, ensuring the safety, efficacy, and regulatory compliance of pharmaceutical products. Conventional analytical techniques such as high-performance liquid chromatography (HPLC) and gas chromatography (GC) provide excellent analytical performance but often require extensive sample preparation, longer analysis times, and substantial solvent consumption. Fourier Transform Infrared (FTIR) spectroscopy has emerged as a rapid, cost-effective, and environmentally friendly alternative for pharmaceutical analysis. This review critically evaluates recent advances in FTIR spectroscopy for the quantitative determination of drug purity in pharmaceutical dosage forms, with particular emphasis on sampling strategies, validation requirements, and chemometric applications. Published studies involving transmission FTIR, attenuated total reflectance (ATR-FTIR), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) are systematically examined and compared. The role of chemometric techniques, including principal component analysis (PCA), partial least squares (PLS) regression, is discussed in overcoming spectral overlap and improving analytical performance. Validation parameters including linearity, accuracy, precision, specificity, limit of detection (LOD), and limit of quantification (LOQ) are critically assessed according to current regulatory guidelines. The reviewed studies demonstrate that FTIR spectroscopy, particularly when integrated with advanced chemometric methods, can provide reliable quantitative analysis of pharmaceutical compounds with analytical performance comparable to conventional techniques. Nevertheless, challenges related to model transferability, standardization, and regulatory acceptance remain. Future developments in machine learning-assisted spectroscopy, portable FTIR instrumentation, and harmonized validation protocols are expected to further expand the role of FTIR spectroscopy in pharmaceutical quality control and counterfeit drug detection.