A rapid, precise, and selective spectroscopic method based on the quantitative proton nuclear magnetic resonance (1H-qNMR) was developed to estimate aspirin and clopidogrel in their pharmaceutical dosages for the first time. The evolved method was utilized to estimate both drugs in presence of the aspirin degradation product, salicylic acid. Moreover, aspirin and clopidogrel were subjected to various stress conditions such as acid hydrolysis, alkali hydrolysis, water hydrolysis, H2O2 oxidation, and photodecomposition for studying the stability of both compounds under these stress conditions. The 1H-qNMR analyses of the analytes of interest were conducted using the internal standard phloroglucinol and the solvent dimethyl sulfoxide-d6. The NMR spectra showed a quantitative doublet of doublets (dd) signal of aspirin at 7.945 ppm, a doublet signal of clopidogrel at 6.875 ppm, and a dd signal of salicylic acid at 7.810 ppm. The internal standard phloroglucinol exhibited a singlet signal at 5.690 ppm. The results demonstrated the linearity (r2 > 0.999), accuracy, precision (RSD < 2.0 %), stability, selectivity, and specificity of the evolved method. Linearity was confirmed in the ranges of 0.05–3.0 mg/mL for aspirin, 0.15–10.0 mg/mL for clopidogrel, and 0.1–5.0 mg/mL for salicylic acid. The evolved method was efficiently applied to analyse aspirin and clopidogrel in their dosages with high %recovery. Moreover, The RGB algorithm technique was used to evaluate the whiteness profile of the suggested method; the findings confirmed the sustainability of the evolved method, which employed an ecological solvent, followed a simple and straightforward procedure, and avoided any pretreatment or labelling stages for the samples. All the aforementioned advantages gave the technique the privilege.
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