Evaluation of six eco-analytical tools for the sustainable HPLC analysis of a quinary anti-cold drug mixture

We present a novel, eco-friendly RP-HPLC method for determining five key components commonly found in anti-cold pharmaceutical formulations simultaneously: Paracetamol (PAR), an analgesic and antipyretic; pseudoephedrine (PSE), an antihistamine; chlorpheniramine (CHL) and preservatives methylparaben (MET) and propylparaben (PRO). In cold medications, these compounds are often incorporated to treat fever, nasal congestion, and allergic rhinitis symptoms. Chromatographic separation was achieved using an Inert Sustain C18 column (250 × 4.6 mm, 5 μm) under gradient elution mode, with a green mobile phase of ethanol and 0.1% trifluoroacetic acid (pH 2.2), a flow rate of 1.0 mL/min, and ambient temperature (25 °C). Detection was performed using PDA with time-programmed wavelength scanning: 214 nm for PSE, 244 nm for PAR, and 264 nm for CHL, MET, and PRO, ensuring optimal sensitivity and selectivity for each analyte. An analysis of the method went beyond its analytical performance by incorporating six advanced sustainability metrics: MoGAPI, Complex MoGAPI, MoGSA, BAGI, RAPI, VIGI, CACI, and GEARS, which are all designed to provide a multidimensional evaluation of factors such as environmental impact, operational efficiency, and innovation. The STABLE toolkit was applied to all compounds to provide quantitative stability scores and identify vulnerabilities under stress conditions. A low toxicity and biodegradable organic solvent, ethanol, was selected for the organic solvent, while trifluoroacetic acid provided optimal peak resolution under acidic conditions. Analytical validation confirmed excellent linearity (r² > 0.999), precision (%RSD < 2%), and sensitivity, in compliance with ICH guidelines. Using sustainable metrics for routine pharmaceutical analysis is an important step toward eco-friendly chromatographic practices, which is pioneered in this study. Furthermore, it fosters responsible innovation in pharmaceutical quality control by ensuring regulatory compliance and analytical reliability.