Complementary spectroscopic methods for simultaneous quantification of tiotropium bromide and olodaterol hydrochloride with analytical performance and environmental sustainability assessment

Abstract The development of efficient, cost-effective, and environmentally friendly analytical methods for drug quality control is essential in modern pharmaceutical analysis. This study presents, to the best of our knowledge, two independent and complementary analytical strategies for the simultaneous quantification of tiotropium bromide (TBM) and olodaterol hydrochloride (OLH) in laboratory-prepared mixtures and the pharmaceutical formulation Stiolto ® Respimat. The first strategy employed UV–Vis spectroscopy combined with Partial Least Squares (PLS), Genetic Algorithm-PLS (GA-PLS), and Multivariate Curve Resolution–Alternating Least Squares (MCR-ALS), whereas the second employed first-derivative Fourier Transform Infrared (FTIR) spectroscopy using zero-crossing wavenumbers. Validation mixtures were designed using Latin Hypercube Sampling to provide systematic coverage of the investigated concentration space. First-derivative preprocessing was applied to enhance spectral resolution and minimize baseline effects. The UV–Vis spectra in the range of 222–263 nm and FTIR spectra in the range of 4000–400 cm⁻¹ were used for quantitative analysis. Among the investigated UV–Vis chemometric models, MCR-ALS provided the lowest root mean square errors of calibration and prediction, with RMSEC and RMSEP values of 0.0359 and 0.0329 for TBM and 0.0622 and 0.0375 for OLH, respectively. The developed models provided recoveries of approximately 100%, with precision expressed as RSD values below 2%. Application to the commercial formulation produced satisfactory recoveries ranging from 98% to 101% for both drugs using the developed techniques. Statistical comparison with the reference HPLC method showed no significant differences at the 95% confidence level. Overall, the complementary UV–Vis chemometric and ATR-FTIR approaches provided satisfactory quantitative performance for the simultaneous determination of TBM and OLH within the investigated analytical ranges.