Vanga Mohan Goud, Bukke Sarad Pawar Naik, Kusuma Praveen Kumar, Narapureddy Bayapa Reddy, Thalluri Chandrashekar
Department of Pharmaceutical Analysis, Joginpally BR Pharmacy College, Hyderabad, Telangana, 500075, India.
Department of Pharmaceutics and Pharmaceutical Technology, Kampala International University, Western Campus, P. O. Box 71, Ishaka-Bushenyi, Uganda.
BMC Chem. 2025 Mar 15;19(1):70. doi: 10.1186/s13065-025-01448-8.
Chronic obstructive pulmonary disease (COPD) is a significant global health issue, worsened by pollution and modernisation. Ensifentrine (EFT), a new dual inhibitor of phosphodiesterase PDE3 and PDE4, is being developed for inhalation to target airway inflammation, bronchodilation, and ciliary function in COPD treatment.
This study aims to develop and validate a new quantification method for Ensifentrine, as no previous techniques are available, by integrating analytical quality-by-design (AQbD) and green analytical chemistry (GAC) principles.
An AQbD framework, utilizing Design-expert software and a central composite design, optimized the RP-UPLC method. The optimized conditions involved isocratic separation on an ACQUITY UPLC HSS C18 SB column at ambient temperature, with a mobile phase of 0.01 N KHPO (pH 5.4) and acetonitrile (66.4:33.6 v/v), a flow rate of 0.27 mL/min, and PDA detection at 272.0 nm.
The statistical analysis confirmed the model's significance and normal distribution. The method, validated according to ICH guidelines, showed good linearity (r = 0.9997) over a range of 3.75-22.5 μg/mL, with an LOD of 3.3 μg/mL and LOQ of 10 μg/mL. It was successfully applied to bulk materials and pharmaceutical formulations with statistical comparisons.
The greenness of the developed method was evaluated using tools such as ComplexMoGAPI, AGREE, BAGI, Green certificate-modified Eco-scale, and ChlorTox Scale. Additionally, the EVG method evaluation tool was also used to assess environmental impact, with the results shown in a radar chart.
This study presents a sensitive and robust RP-UPLC method for quantifying Ensifentrine, combining AQbD and GAC principles. The method, validated according to ICH guidelines, also ensures environmental sustainability. This approach sets a precedent for future analytical method development in pharmaceutical sciences with a focus on sustainability.
慢性阻塞性肺疾病（COPD）是一个重大的全球健康问题，污染和现代化使其恶化。恩昔芬净（EFT）是一种新型磷酸二酯酶PDE3和PDE4双重抑制剂，正在开发用于吸入给药，以针对COPD治疗中的气道炎症、支气管扩张和纤毛功能。
由于之前没有可用的技术，本研究旨在通过整合分析质量源于设计（AQbD）和绿色分析化学（GAC）原则，开发并验证一种新的恩昔芬净定量方法。
采用Design-expert软件和中心复合设计的AQbD框架优化反相超高效液相色谱（RP-UPLC）方法。优化条件包括在室温下于ACQUITY UPLC HSS C18 SB柱上进行等度分离，流动相为0.01 N KHPO（pH 5.4）和乙腈（66.4:33.6 v/v），流速为0.27 mL/min，在272.0 nm处进行光电二极管阵列（PDA）检测。
统计分析证实了模型的显著性和正态分布。该方法根据国际人用药品注册技术协调会（ICH）指南进行验证，在3.75 - 22.5 μg/mL范围内显示出良好的线性（r = 0.9997），检测限（LOD）为3.3 μg/mL，定量限（LOQ）为10 μg/mL。通过统计比较，该方法成功应用于原料药和药物制剂。
使用ComplexMoGAPI、AGREE、BAGI、绿色证书修正的生态规模和ChlorTox Scale等工具评估所开发方法的绿色程度。此外，还使用EVG方法评估工具评估环境影响，结果以雷达图显示。
本研究提出了一种结合AQbD和GAC原则的灵敏且稳健的RP-UPLC方法用于定量恩昔芬净。该方法根据ICH指南进行验证，还确保了环境可持续性。这种方法为药物科学中未来注重可持续性的分析方法开发树立了先例。
