Abdallah Nora A, Elmansi Heba, Alossaimi Manal A, Altamimi Abdulmalik S A, El Abass Samah Abo, Elama Heba Samir
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Pharmaceutical Chemistry Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Spectrochim Acta A Mol Biomol Spectrosc. 2026 Jan 15;345:126769. doi: 10.1016/j.saa.2025.126769. Epub 2025 Aug 5.
One of the most commonly prescribed medications are antithrombotic agents which consisting of antiplatelet and anticoagulant medications. Currently, millions of patients rely on them to avoid blood-clot-related issues across various cardiovascular diseases. The combined administration of apixaban, aspirin and clopidogrel is an example of this therapy which can be used for the risk reduction in cardiovascular death. The importance of such medications encourages us to investigate novel analytical assay methods for determination of such drugs in dosage forms as well as in human plasma. Spectroscopic technique was the best choice to design new analytical methods due to its applicability and simplicity. Three spectroscopic methods were introduced for concurrent determination of apixaban, aspirin and clopidogrel. The designed methods were; A direct measurement for determination of apixaban without interference from the other two drugs (method I), Ratio spectra (method II) and first derivative ratio spectra (method III). The first method enables us to determine apixaban through direct measurement of its absorption spectrum at 310 nm with no reading from aspirin or clopidogrel. Ratio spectra method (method II) was performed at ΔP = 223.6-245.2 nm for aspirin, ΔP = 293.2-307.0 nm for apixaban and ΔP = 251.0-260.0 nm for clopidogrel. The third first derivative ratio spectra method was based on measuring apixaban at 255 nm, aspirin at 242 nm and clopidogrel at 260 nm using the other two analytes as a double divisor. The linearity of the designed methods was 0.5-18 μg/mL for apixaban by the three methods while were 2.0-28 μg/mL for both aspirin and clopidogrel by method II & III. These developed approaches were effectively applied for estimation of the three studied drugs in their raw materials, synthetic mixtures and dosage forms simultaneously. The co-administration of these treatments enables us to extend the application for determination of them in spiked human plasma without complicated procedures. The applied methods were validated following the ICH Q2(R1) guidelines. The greenness of the designed methods was evaluated using six different tools including; Analytical Eco-scale, GAPI, AGREE metrics, NEMI, whiteness and blueness assessment.
最常用的药物之一是抗血栓形成剂，它由抗血小板药物和抗凝药物组成。目前，数百万患者依靠它们来避免各种心血管疾病中与血栓相关的问题。阿哌沙班、阿司匹林和氯吡格雷的联合给药就是这种疗法的一个例子，可用于降低心血管死亡风险。这类药物的重要性促使我们研究用于测定剂型以及人血浆中此类药物的新型分析测定方法。光谱技术因其适用性和简便性，是设计新分析方法的最佳选择。介绍了三种用于同时测定阿哌沙班、阿司匹林和氯吡格雷的光谱方法。所设计的方法有：直接测量法（方法I），用于测定阿哌沙班，不受其他两种药物干扰；比率光谱法（方法II）；一阶导数比率光谱法（方法III）。第一种方法使我们能够通过直接测量阿哌沙班在310nm处的吸收光谱来测定它，而无需读取阿司匹林或氯吡格雷的读数。比率光谱法（方法II）中，阿司匹林的ΔP为223.6 - 245.2nm，阿哌沙班的ΔP为293.2 - 307.0nm，氯吡格雷的ΔP为251.0 - 260.0nm。第三种一阶导数比率光谱法是基于以其他两种分析物作为双除数，在255nm处测量阿哌沙班、在242nm处测量阿司匹林、在260nm处测量氯吡格雷。三种方法测定阿哌沙班的线性范围均为0.5 - 18μg/mL，方法II和III测定阿司匹林和氯吡格雷的线性范围均为2.0 - 28μg/mL。这些开发的方法有效地应用于同时测定原料药、合成混合物和剂型中三种研究药物的含量。这些治疗方法的联合应用使我们能够在不进行复杂操作的情况下，将它们在加标人血浆中的测定应用范围扩大。所应用的方法按照ICH Q2(R1)指南进行了验证。使用六种不同工具评估了所设计方法的绿色度，包括：分析生态规模、GAPI、AGREE指标、NEMI、白度和蓝度评估。
