Ali Salma N, Saad Samah S, Fayed Ahmed S, Marzouk Hoda M
Pharmaceutical Analytical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science & Technology, 6th of October City, Giza, Egypt.
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Al-Aini Street, Cairo, 11562, Egypt.
BMC Chem. 2024 Aug 27;18(1):157. doi: 10.1186/s13065-024-01265-5.
Ipratropium bromide (IPR) and fenoterol hydrobromide (FEN) have recently been combined in a promising inhaler to treat two prevalent inflammatory illnesses of the airways: bronchial asthma and chronic obstructive pulmonary disease (COPD). The necessity for a single, sensitive, and trustworthy analytical approach to cover the diverse and necessary tests of in-vitro and in-vivo studies is greatly grown with the rising production of new fixed combinations. Two novel, selective and environmentally friendly LC techniques were developed in order to guarantee precise measurement of IPR and FEN in their challenging formulation. The initial technique involved high-performance thin-layer chromatography (HPTLC) in conjunction with densitometric quantification. Chromatographic separation was attained on HPTLC plates utilizing ethyl acetate - ethanol - acetic acid (5.0:5.0:0.1, by volume) as a developing system. Densitometric quantification of the separated bands was carried out at 220.0 nm over concentration ranges of 0.50-15.0 µg/band for IPR and 0.50-12.0 µg/band for FEN. High-performance liquid chromatography (HPLC) paired with diode array detection (DAD) was the core of the second technique. The optimized separation was achieved on a Zorbax SB C (150 × 4.6 mm, 5 μm) column with a combination of 10.0 mM potassium dihydrogen orthophosphate, pH 5.0 ± 0.1, adjusted with o-phosphoric acid and methanol (70:30, v/v) as the mobile phase and pumped at flow rate of 1.0 mL/min. The peaks were monitored at 220.0 nm using diode array detection, achieving linearity range of 5.0-200.0 µg/mL for both drugs. The ICH criteria have been verified and both methods have been confirmed to be valid, and successfully applied for assay the cited drugs in the Atrovent comp HFA metered dose inhaler as well as delivered dose uniformity testing of the final product. Finally, whiteness appraisal and several state-of-the-art green evaluation metrics were applied to evaluate the sustainability of the proposed methods. The suggested approaches produced promising results and are the first simple and sustainable methodologies for the simultaneous quantification of both drugs in different real samples, all of which strongly suggest their application in quality control laboratories.
异丙托溴铵（IPR）和氢溴酸非诺特罗（FEN）最近被组合在一种很有前景的吸入器中，用于治疗两种常见的气道炎症性疾病：支气管哮喘和慢性阻塞性肺疾病（COPD）。随着新型固定组合产品产量的增加，对于一种单一、灵敏且可靠的分析方法以涵盖体外和体内研究的各种必要测试的需求大幅增长。为了确保在具有挑战性的制剂中精确测量IPR和FEN，开发了两种新颖、选择性且环保的液相色谱技术。第一种技术涉及高效薄层色谱（HPTLC）结合密度定量法。在HPTLC板上进行色谱分离，使用乙酸乙酯 - 乙醇 - 乙酸（体积比5.0:5.0:0.1）作为展开系统。对分离的条带进行密度定量，在220.0 nm处，IPR的浓度范围为0.50 - 15.0 μg/条带，FEN的浓度范围为0.50 - 12.0 μg/条带。第二种技术的核心是高效液相色谱（HPLC）与二极管阵列检测（DAD）联用。在Zorbax SB C（150×4.6 mm，5 μm）柱上实现了优化分离，流动相为10.0 mM磷酸二氢钾（用邻磷酸调节pH至5.0±0.1）和甲醇（70:30，v/v）的组合，流速为1.0 mL/min。使用二极管阵列检测在220.0 nm处监测峰，两种药物的线性范围均为5.0 - 200.0 μg/mL。已验证符合国际协调会议（ICH）标准，两种方法均被确认为有效，并成功应用于测定爱全乐复方氢氟烷计量吸入器中所述药物以及最终产品的递送剂量均匀性测试。最后，应用白度评估和几种最先进的绿色评估指标来评估所提出方法的可持续性。所建议的方法产生了有前景的结果，是首次用于同时定量不同实际样品中两种药物的简单且可持续的方法，所有这些都强烈表明它们可应用于质量控制实验室。
