Chanduluru Hemanth Kumar, Sugumaran Abimanyu
SRM College of Pharmacy, SRM Institute of Science and Technology Kattankulathur- 603203 India
RSC Adv. 2021 Sep 7;11(45):27820-27831. doi: 10.1039/d1ra04843k. eCollection 2021 Aug 16.
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. This technique was validated and established a linearity range of 10-60 μg mL and 18.75-112.5 μg mL, with 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.
硝酸异山梨酯（ISD）和盐酸肼屈嗪（HDZ）是治疗心力衰竭的关键药物。目前，根据文献，尚无结合超高效液相色谱法（UPLC）和绿色分析质量源于设计的方法来测定ISD和HDZ，而这对于设计一种可长期持续使用的方法至关重要。本研究提出了一种基于绿色分析质量源于设计的UPLC方法，用于对硝酸异山梨酯（ISD）和盐酸肼屈嗪（HDZ）进行环保型测定。所开发的技术能够使用含乙醇和0.1%三氟乙酸（60∶40% v/v）的菲罗门C18（50×2.1 mm，2μm）色谱柱，以0.5 mL/min的流速分离ISD和HDZ及其降解产物。该技术经过验证，建立了10 - 60 μg/mL和18.75 - 112.5 μg/mL的线性范围，ISD和HDZ的相关系数分别为0.9998和0.9992，同时具备准确性、重现性和选择性。采用国家环境方法指数、分析生态量表、绿色分析程序指数、分析方法绿色度评分和分析绿色度指标等五种不同评估技术对新方法进行了进一步评估，结果表明该方法对环境无害。基于这些结果，我们得出结论，所开发的结合绿色分析质量源于设计方法用于测定稳定性的UPLC技术，可能有助于新型药物产品如硝酸异山梨酯和肼屈嗪的研发。
