Soliman Rabab M, Mostafa Nadia M, Fayez Yasmin M, Monir Hany H, Rostom Yasmin
Ministry of Health and Population, Directorate of Health Affairs, Ismailia Health Administration, Ismailia, Egypt.
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562 Cairo, Egypt.
Spectrochim Acta A Mol Biomol Spectrosc. 2025 Feb 15;327:125381. doi: 10.1016/j.saa.2024.125381. Epub 2024 Nov 2.
Recently, cold and cough dosage forms have gained significant attention due to their use in the supportive protocols for managing COVID-19 symptoms. In this study, a pharmaceutical formulation containing Paracetamol (PAR), Guaifenesin (GUA), and Phenylephrine hydrochloride (PHE) was investigated for spectral resolution and quantification using advanced spectrophotometric methods. The spectra of these components were significantly overlapped and present in their combined tablet in a challenging ratio of 250:100:5 for PAR, GUA, and PHE, respectively. The established approaches were employed for the simultaneous determination of these drugs in their pharmaceutical formulation without interference from matrix excipients. The study involved various manipulation steps, allowing each component in the combination to be analyzed by more than one approach. Integrating these methods with smart mathematical techniques, the issue of spectral data overlap was resolved without the need for preliminary separation steps. The developed methods are dual wavelength, first derivative, derivative ratio, ratio difference, constant center coupled with spectrum subtraction, and constant multiplication paired with spectrum subtraction. The proposed methods were linear over the concentration range of 3.0-35.0 μg/mL for GUA and 3.0-30.0 μg/mL for PHE. While the PAR ranges for the first derivative and constant multiplication methods were 2.5-35.0 μg/mL and 2.5-25.0 μg/mL, respectively. Excellent linearity of the suggested methods was demonstrated by the high correlation coefficients (R2), ≥ 0.9998 for all the tested compounds. These methodologies were validated according to ICH guidelines. Validation results demonstrated excellent accuracy, with recovery percentages ranging from 98 to 102 %, and precision, with RSD values less than 2 %. The obtained results were statistically compared with the official ones using F-test, Student's t-test, and one-way ANOVA, revealing no significant differences. The proposed methods are accurate, green, smart, fast, and cost-effective. Their compliance with Green Analytical Chemistry principles was evaluated and compared to a published method using various tools to enable a more holistic evaluation from different perspectives. The promising results revealed that the investigated methods are superior green alternatives for routine analysis of the cited drugs in laboratories with limited resources and without access to expensive instruments.
最近，感冒和咳嗽剂型因其在管理新冠病毒症状的支持性方案中的应用而备受关注。在本研究中，使用先进的分光光度法对一种含有对乙酰氨基酚（PAR）、愈创甘油醚（GUA）和盐酸去氧肾上腺素（PHE）的药物制剂进行了光谱分辨率和定量研究。这些成分的光谱有显著重叠，且在其复方片剂中的比例分别为PAR、GUA和PHE的250:100:5，极具挑战性。所建立的方法用于同时测定其药物制剂中的这些药物，不受基质辅料的干扰。该研究涉及多个操作步骤，使组合中的每种成分都能通过多种方法进行分析。将这些方法与智能数学技术相结合，无需初步分离步骤即可解决光谱数据重叠问题。所开发的方法包括双波长、一阶导数、导数比、比值差、恒定中心结合光谱减法以及恒定乘法结合光谱减法。所提出的方法在愈创甘油醚浓度范围为3.0 - 35.0μg/mL、盐酸去氧肾上腺素浓度范围为3.0 - 30.0μg/mL时呈线性。而一阶导数法和恒定乘法法中对乙酰氨基酚的浓度范围分别为2.5 - 35.0μg/mL和2.5 - 25.0μg/mL。所有测试化合物的高相关系数（R2）≥0.9998，证明了所建议方法具有出色的线性。这些方法按照国际人用药品注册技术协调会（ICH）指南进行了验证。验证结果表明准确性极佳，回收率在98%至102%之间，精密度良好，相对标准偏差（RSD）值小于2%。使用F检验、学生t检验和单因素方差分析将所得结果与官方结果进行统计学比较，未发现显著差异。所提出的方法准确、绿色、智能、快速且具有成本效益。使用各种工具对其符合绿色分析化学原则的情况进行了评估，并与已发表的方法进行了比较，以便从不同角度进行更全面的评估。有前景的结果表明，在所研究的资源有限且无法使用昂贵仪器的实验室中，这些方法是对上述药物进行常规分析的优越绿色替代方法。
