Eco-friendly estimation of isosorbide dinitrate and hydralazine hydrochloride using Green Analytical Quality by Design-based UPLC Method

Abstract

Isosorbide dinitrate (ISD) and hydralazine hydrochloride (HDZ) are critical drugs for the treatment of heart failure. Currently, no available analytical method for the determination of ISD and HDZ exists as per the literature that combines UPLC and Green Analytical Quality by Design, which is critical for designing a method that is sustainable for long-term use. This study proposes an eco-friendly determination of isosorbide dinitrate (ISD) and hydralazine hydrochloride (HDZ) using a Green Analytical Quality by Design-based UPLC Method. The developed technique is capable of separating ISD and HDZ, as well as their degradation products, using a Phenomenex C18 (50 × 2.1 mm, 2 μm) column containing ethanol and 0.1% trifluoroacetic acid (60 : 40% v/v) at a flow rate of 0.5 mL min⁻¹. This technique was validated and established a linearity range of 10–60 μg mL⁻¹ and 18.75–112.5 μg mL⁻¹, with R² of 0.9998 and 0.9992 for ISD and HDZ, respectively along with accuracy, reproducibility, and selectivity. The new approach was further evaluated using five different assessment techniques such as National Environmental Methods Index, Analytical Eco-Scale, Green Analytical Procedure Index, Analytical Method Greenness Score, and Analytical GREEnness Metrics, and was determined to be environmentally benign. Based on these results, we have concluded that the developed UPLC technique with the combined approach of Green Analytical Quality by Design for determining stability might benefit in the creation of novel pharmaceutical products such as isosorbide dinitrate and hydralazine.