# Computer aided greenness by design approach for resolving and quantifying Triamterene and Hydrochlorothiazide in pharmaceutical mixtures employing multiscale dynamics simulations

## TL;DR

This paper introduces a greener analytical method using simulations to determine two drugs in mixtures, reducing solvent waste and improving efficiency.

## Contribution

The study introduces a Greenness-by-Design approach combining multiscale simulations and UV spectroscopy for pharmaceutical analysis.

## Key findings

- The method uses a compromise solvent to minimize peak broadening and improve spectral resolution.
- The developed methods achieved detection limits as low as 0.255 µg/mL for Hydrochlorothiazide and 0.516 µg/mL for Triamterene.
- A greenness assessment confirmed the sustainability of the proposed analytical methods.

## Abstract

In this study, we present an established approach for the UV spectroscopic determination of Hydrochlorothiazide and Triamterene in pharmaceutical mixtures, leveraging the principles of Greenness-by-Design (GbD). By integrating molecular and electronic dynamics simulations, we have developed a greener analytical methodology that significantly reduces time and solvent waste. Our approach focuses on selecting a compromise solvent to minimize peak broadening, thereby enhancing spectral resolution and simplifying the analytical process. This work extends our ongoing efforts to establish the GbD concept in analytical chemistry, building on our previous research to promote sustainable and efficient analytical practices. The developed methods are based on simple mathematical manipulations, including Fourier self-deconvolution, absorption correction, and isoabsorptive point methods, along with ratio spectra approaches such as ratio difference and ratio derivative spectrophotometric methods. The Hydrochlorothiazide and Triamterene were determined with linear ranges of (1–18) µg/mL and (1–14) µg/mL, respectively. The detection and quantitation limits were in the range of (0.255–0.640) µg/mL, and (0.516–1.359) µg/mL, which reflects the method’s sensitivity. Moreover, a greenness assessment was performed to evaluate the sustainability of the proposed methods, indicating greener outcomes with a considerable reduction of the ecological footprint. This comprehensive approach underscores the potential of GbD in developing efficient, greener analytical methodologies for pharmaceutical analysis.

The online version contains supplementary material available at 10.1038/s41598-025-13486-2.