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Abstract The availability of well-established analytical methods is crucial to cope with the fast-ongoing research for the development of new drug delivery formulations. In this work, a rapid highly green chromatographic method was developed for the simultaneous determination of nicotine (NIC) and caffeine (CAF) to be applied for an in-vitro release study from a newly prepared quick mist mouth spray co-formula (QMS), as a complementary synergistic fast-onset relief of cravings during smoking cessation. The chromatographic resolution was accomplished on a cyano column using isocratically delivered (1.0 mL/ min) glycerol: orthophosphoric acid (OPA) (0.2 M) adjusted to pH 3.0 using 0.05 M triethylamine (5:95, v/v) and UV detection at 260 nm. Well resolved peaks of NIC and CAF were eluted at 2.1 and 3.9 min (Rs = 5.64), with linear responses between 0.1 and 20.0 µg/mL and 0.2–40.0 µg/mL, and detection limits of 0.03 and 0.07 µg/mL for NIC and CAF, respectively. The developed method showed good analytical performance (accuracy, precision, robustness, and selectivity) as well as superiority in practicality and ecological profile compared to reported methods applying GAPI, analytical eco-scale, AGREE, BAGI, and whiteness metric tool. The developed method was successfully applied for NIC and CAF determination in their pharmaceutical preparations, and artificial saliva with no significant differences from reported method results (F-test and t-test). Moreover, an in-vitro release study of NIC and CAF from QMS was performed employing the developed method that revealed diffusion-controlled release, compared to mixed diffusion/ polymer chain relaxation for marketed single component formulation, showing the superiority of QMS in reducing drug level fluctuations of NIC and CAF and improving their bioavailability. Graphical Abstract

Abstract The development of sustainable analytical methodologies that minimize hazards, waste generation, and energy consumption has become crucial. This study introduces pioneering green‒blue-white approaches for the simultaneous quantification of montelukast sodium (MLK) and fexofenadine hydrochloride (FEX) in combination formulations. The first approach employs an ultra-performance liquid chromatographic method (UPLC) with a green micellar mobile phase of 0.02 M sodium dodecyl sulfate and 10% 1-pentanol (65:35%). The method demonstrated excellent resolution, peak symmetry, and a short analysis time, with retention times of 3.53 min for MLK and 1.67 min for FEX. The MLK and FEX linearities were 1–260 and 1.2–312 μg/mL, respectively. The second approach involves complementary built-in spectroscopic techniques (second derivative, third derivative, and ratio difference methods) using water as a solvent, providing a green, simple, low-cost alternative in laboratories where expensive chromatographic devices may not be readily available. The MLK and FEX linearities were 3–50 and 3–60 μg/mL, respectively. All methods were comprehensively validated and showed satisfactory results. The proposed methods demonstrated excellent linearity (r2 ≥ 0.9990), accuracy (recovery 98.5–101.5%), and precision (RSD ≤ 2%) across wide concentration ranges. A multifaceted evaluation was conducted to assess the environmental sustainability, real-world applicability, and economic viability of the proposed methods in comparison with previously reported techniques. This comprehensive assessment leveraged several state-of-the-art tools, including NEMI, ComplexGAPI, AGREE, ESA, BAGI, and RGB12. The suggested approaches exhibited favorable quadrant profiles in the NEMI and ComplexGAPI assessments, coupled with higher AGREE scores (0.90, 0.86) than reported (0.62, 0.74, 0.75, 0.69, 0.74, 0.74, and 0.75), in addition to higher ESA score (88, 92) than reported (75, 84, 85, 79, 82, 82, and 83), collectively affirming their environmentally friendly credentials. Moreover, we embraced the innovative notions of 'blueness' and 'whiteness' assessment by harnessing the recently formulated BAGI and RGB12 algorithms. The higher BAGI score (90, 82.5) than reported (72.5, 70, 70, 67.5, 67.5, 67.5, and 72.5), confirmed the excellent real-world applicability of the proposed methods, while the notable RGB12 indices (89.8, 88.1) than reported (67.8, 72.8, 71.5, 67.1, 73.7, 70.3, and 73.2), validated their cost-effectiveness and overall sustainability, contributing to an eco-friendly future for quality control processes.

Abstract Developing analytical techniques that align with green and sustainable chemistry principles is crucial in today's scientific landscape. This work introduces two innovative approaches for the simultaneous quantification of indacaterol (IND) and mometasone (MOM), a recently approved combination therapy for chronic obstructive pulmonary disease. These methods—rapid isocratic ion pair chromatography (IPC) and UV–visible spectrophotometry—demonstrate improved environmental sustainability, cost-effectiveness, and versatility compared to existing techniques. The optimized 4-min IPC method achieved excellent resolution (retention times 2.18 ± 0.1 min for IND and 3.95 ± 0.1 min for MOM), peak symmetry, and sensitivity. It utilizes a low-cost ion pair mobile phase of acetonitrile and acidified water containing 0.025% sodium dodecyl sulfate (50:50% v/v), making it suitable for laboratories with standard chromatographic instruments. The spectrophotometric approach offers two procedures: first derivative and ratio derivative methods. These serve as simplified, low-cost alternatives for resource-limited laboratories without access to advanced instruments. Both techniques feature simplified protocols that minimize extraction and fractionation steps. Comprehensive validation confirmed outstanding accuracy (98–102%) and precision (%2

Abstract Montelukast sodium (MLK) and Levocetirizine dihydrochloride (LCZ) are widely prescribed medications with promising therapeutic potential against COVID-19. However, existing analytical methods for their quantification are unsustainable, relying on toxic solvents and expensive instrumentation. Herein, we pioneer a green, cost-effective chemometrics approach for MLK and LCZ analysis using UV spectroscopy and intelligent multivariate calibration. Following a multilevel multifactor experimental design, UV spectral data was acquired for 25 synthetic mixtures and modeled via classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm-PLS (GA-PLS) techniques. Latin hypercube sampling (LHS) strategically constructed an optimal validation set of 13 mixtures for unbiased predictive performance assessment. Following optimization of the models regarding latent variables (LVs) and wavelength region, the optimum root mean square error of cross-validation (RMSECV) was attained at 2 LVs for the 210–400 nm spectral range (191 data points). The GA-PLS model demonstrated superb accuracy, with recovery percentages (R%) from 98 to 102% for both analytes, and root mean square error of calibration (RMSEC) and prediction (RMSEP) of (0.0943, 0.1872) and (0.1926, 0.1779) for MLK and LCZ, respectively, as well bias-corrected mean square error of prediction (BCMSEP) of -0.0029 and 0.0176, relative root mean square error of prediction (RRMSEP) reaching 0.7516 and 0.6585, and limits of detection (LOD) reaching 0.0813 and 0.2273 for MLK and LCZ respectively. Practical pharmaceutical sample analysis was successfully confirmed via standard additions. We further conducted pioneering multidimensional sustainability evaluations using state-of-the-art greenness, blueness, and whiteness tools. The method demonstrated favorable environmental metrics across all assessment tools. The obtained Green National Environmental Method Index (NEMI), and Complementary Green Analytical Procedure Index (ComplexGAPI) quadrants affirmed green analytical principles. Additionally, the method had a high Analytical Greenness Metric (AGREE) score (0.90) and a low carbon footprint (0.021), indicating environmental friendliness. We also applied blueness and whiteness assessments using the high Blue Applicability Grade Index (BAGI) and Red–Green–Blue 12 (RGB 12) algorithms. The high BAGI (90) and RGB 12 (90.8) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability. This work puts forward an optimal, economically viable green chemistry paradigm for pharmaceutical quality control aligned with sustainable development goals.