Ministry of Health and Population, Directorate of Health Affairs, Ismailia Health Administration, Ismailia, Egypt.
Cairo University, Faculty of Pharmacy, Analytical Chemistry Department, Kasr El-Aini Street, Cairo 11562, Egypt.
J AOAC Int. 2022 Sep 6;105(5):1268-1279. doi: 10.1093/jaoacint/qsac031.
Common cold and cough preparations represent a huge segment of the global pharmaceutical market. Recently, cold/cough formulations containing paracetamol (PAR) have attracted significant attention as PAR has been implemented into the supportive treatment of mild cases of COVID-19 as the first-line antipyretic. From a literature review, no method has been reported yet for simultaneous estimation of PAR, pseudoephedrine hydrochloride (PSE) and carbinoxamine maleate (CRX) in any matrix. Thus, there is an urgent need for smart and green methods that would enable quantification of the cited components in their challenging ratio.
The aim of this work is to develop and validate the first UV spectrophotometric methods for simultaneous determination of the selected drugs taking into consideration the list of challenges including the highly overlapping features and spectral interferences in the cited mixture.
Namely, the proposed methods are: direct spectrophotometry, dual wavelength, first derivative, derivative ratio, ratio difference, constant center coupled with spectrum subtraction, and the constant multiplication method paired with spectrum subtraction.
These methods were linear over the concentration range of 2.5-35, 1.5-20, and 4.5-35 μg/mL for PAR, PSE and CRX, respectively. These methods fulfill the validity parameters according to International Conference on Harmonization (ICH) guidelines. The results obtained were statistically benchmarked to the official ones where no significant difference was noticed.
The developed methods are successfully applied for concurrent quantification of the studied components in the marketed dosage form without interference from matrix excipients. The impact on the environment was assessed by five green metrics, namely a recent Analytical greenness (AGREE) metric algorithm based on the green analytical chemistry framework, Green Analytical Procedure Index (GAPI), Eco-Scale, Assessment of Green Profile (AGP), and National Environmental Methods Index (NEMI).
Eco-friendly and successive spectrophotometric methods were firstly developed in this work, for the simultaneous quantification of PAR, PSE and CRX. These approaches incorporate a simple enrichment-aided technique to augment their spectrophotometric signals, facilitating the accurate quantitation of the minor component in the cited mixture.
普通感冒和咳嗽制剂代表了全球制药市场的一个巨大部分。最近，含有对乙酰氨基酚（PAR）的感冒/咳嗽配方引起了广泛关注，因为 PAR 已被纳入 COVID-19 轻度病例的支持性治疗中，作为一线退热剂。从文献综述来看，目前尚未有方法报道可在任何基质中同时测定 PAR、盐酸伪麻黄碱（PSE）和马来酸卡比沙明（CRX）。因此，迫切需要智能和绿色的方法来定量测定所述成分的挑战性比例。
本工作旨在开发和验证第一种紫外分光光度法，同时测定选定药物，考虑到包括在引用混合物中高度重叠特征和光谱干扰在内的一系列挑战。
即提出的方法有：直接分光光度法、双波长法、一阶导数法、导数比法、比值差法、常数中心耦合与光谱减法、常数乘法与光谱减法。
这些方法在 PAR、PSE 和 CRX 的浓度范围分别为 2.5-35、1.5-20 和 4.5-35μg/mL 时呈线性。这些方法符合国际协调会议（ICH）指南的有效性参数。所得结果与官方结果进行了统计学比较，未发现显著差异。
所开发的方法成功地应用于市售制剂中研究成分的同时定量，无基质赋形剂干扰。通过五个绿色指标评估对环境的影响，即基于绿色分析化学框架的最新分析绿色度（AGREE）指标算法、绿色分析程序指数（GAPI）、生态规模、绿色概况评估（AGP）和国家环境方法指数（NEMI）。
本工作首次开发了生态友好且连续的分光光度法，用于同时定量测定 PAR、PSE 和 CRX。这些方法采用简单的富集辅助技术来增强其分光光度信号，有利于准确测定引用混合物中的微量成分。
