Spectral residual augmented classical least squares for simultaneous green determination of cetirizine, fexofenadine and loratadine by UV spectrophotometry in pharmaceuticals and environmental samples.

内容摘要

Second-generation antihistamines-cetirizine, fexofenadine, and loratadine-require simultaneous determination methods for pharmaceutical quality control including cleaning validation and cross-contamination monitoring in multi-product manufacturing facilities, yet their severely overlapping UV spectra preclude direct spectrophotometric quantification. This study developed a novel, sustainable UV-spectrophotometric method employing spectral residual augmented classical least squares (SRACLS) chemometrics to mathematically resolve spectral overlap and enable simultaneous quantification. Calibration (25 mixtures, partial factorial design) and validation sets (20 mixtures, central composite design) spanned 4-12 µg/mL concentration ranges. Comparative evaluation revealed that SRACLS demonstrated superior performance versus concentration residual augmented classical least squares (CRACLS), achieving 40-70% lower prediction errors (RRMSEP: 1.745, 2.605, 1.736 versus 3.011, 3.960, 2.674) and tighter residual distributions (± 3-5 versus ± 5-6 units). Subsequently, ICH Q2(R2) validation confirmed excellent analytical performance: recoveries 98.06-101.95% across the full working range, intra-day precision ≤ 1.522% RSD, inter-day precision ≤ 1.986% RSD, LOD values of 0.379-0.560 µg/mL, LOQ values of 1.149-1.697 µg/mL, and robust selectivity against pharmaceutical excipients and environmental co-contaminants (96.05-103.38% recovery). Application to commercial tablets yielded results statistically equivalent to reported HPLC methods (t-test, F-test: p > 0.05), whereas analysis of tap water samples spiked at concentrations relevant to pharmaceutical manufacturing facility effluents following salting-out assisted liquid-liquid extraction achieved 95.43-103.85% recovery. Moreover, comprehensive sustainability assessment demonstrated excellent performance: MoGAPI 76, CaFRI 85, AGSA 70.83, BAGI 77.5, CACI 66, and AMRI 68, attributed to eliminated organic solvent consumption, minimal energy usage, low waste generation, and high throughput (> 30 samples/hour). Overall, this work represents the first SRACLS application to antihistamine analysis, providing a practical green alternative to chromatographic methods for pharmaceutical quality control and manufacturing effluent monitoring applications.