• Novel and sustainable spectrophotometric techniques for the simultaneous determination of ternary mixture, without prior separation steps. • These techniques resolved severely or partially overlapped peaks successively using consecutive spectra or progressively on the same spectrum. • AI-evaluation of efficiency of spectrophotometric methods enable precise determination of CAR, HCT along with toxic impurity; DSA. • The proposed methods showed good selectivity in laboratory-prepared mixtures and pharmaceutical formulations without interference from excipients. • Specialized assessment tools are utilized to assess the reliability, applicability and sustainability of the proposed methods. This study explores the innovative spectrophotometric methods enhanced with artificial intelligence (AI) driven techniques for the precise detection of compounds carvedilol (CAR) and hydrochlorothiazide (HCT) in combined medicine which is regarded one of the most effective therapies for hypertensive patients who have diabetes, and in presence of potential hydrochlorothiazide correlated impurity; salamide (4-amino-6-chlorobenzene-1,3-disulphonamide) (DSA). The applicability of these methods is evaluated through comprehensive validation parameters, while AI-driven algorithms are assessed for their efficiency regarding data analysis of the obtained results. This study demonstrates applicable, sustainable, reliable and green spectrophotometric methods via factorized response spectrum without prior separation. The factorized response spectrum is the backbone of this unique integrated solution leading to complete resolving of the suggested analytes in the mixture. Thus, the concentrations of the target drugs could be determined separately at their maxima. The developed approaches based on three successive methods namely, simultaneous absorbance resolution (SAR) coupled with absorbance resolution (AR) and spectrum subtraction (SAR-AR-SS), simultaneous amplitude difference with ratio extraction and spectrum subtraction (SAD-RE-SS), and dual amplitude difference with ratio extraction and spectrum subtraction (DAD-RE-SS). These approaches were employed to quantify the investigated drugs in their pure forms in range 4.0-40.0 µg/mL at 285.5 nm for CAR, 2.0- 20.0 µg/mL at 270.5 nm for HCT, and 2.0- 16.0 µg/mL at 265.7 nm for DSA. In accordance with ICH criteria, the aforementioned procedures were validated. These techniques could generally be used successfully for the standard quality control testing of raw drug forms and market-available products. Furthermore, applicability profile, ecological sustainability, reliability, and sustainability of the suggested methods were ensured via utilizing various applicability, greenness, redness, and sustainability assessment tools named: click analytical chemistry index (CACI), blue applicability grade index (BAGI),analytical GREEnness (AGREE), AGREEprep, modified green analytical procedure index (MoGAPI), analytical green star area (AGSA), carbon footprint reduction index (CaFRI), Analytical Method Reliability Index (AMRI), Red Analytical Performance Index (RAPI), and Sustainability of Analytical Methods Index (SAMI) and compared among official and reported methodologies.
Nabil et al. (Fri,) studied this question.