Nano-scale multi-spectroscopic analysis of the anti-fibromyalgia drug pregabalin based on dihydropyridine ring formation with sustainability and whiteness evaluation

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 325; p. 125151
• Main Authors: El Hamd, Mohamed A., Obaydo, Reem H., Ibrahim Helmy, Marwa, Mahdi, Wael A., Alshehri, Sultan, El-Maghrabey, Mahmoud, Nessim, Christine K.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.01.2025
• Subjects: Colorimetry - methods; Cyclization reaction; Dihydropyridine; Dihydropyridines - chemistry; Fibromyalgia - drug therapy; Fluorimetric assay; Formaldehyde - analysis; Formaldehyde - chemistry; Humans; Limit of Detection; Need Quality Sustainability (NQS); Pentanones - chemistry; Pregabalin; Pregabalin - analysis; Pregabalin - chemistry; Reproducibility of Results; Spectrometry, Fluorescence - methods; Urine samples; Urine samples; Pregabalin; Dihydropyridine; Cyclization reaction; Fluorimetric assay; Need Quality Sustainability (NQS)
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2024.125151

[Display omitted] •Multiple-spectroscopic assay of the non-chromophoric zwitterionic drug pregabalin.•Employing Hantzsch’s one-pot cyclization reaction in aqueous conditions.•Formed dihydropyridine derivative was measured colorimetrically and fluorometrically.•The method showed excellent sensitivity down to nanoscale level of 10 ng/mL.•The suggested techniques demonstrated good applicability in pharmaceutical and bioanalysis.•The first spectroscopy study applied the need, quality, and sustainability (NQS) index. This research addresses the challenge of analyzing pregabalin, a primary amine in a zwitterionic structure, which is difficult to evaluate due to its lack of chromatophore. The study introduces a derivatization assessment using Hantzsch’s multicomponent organic reaction to enhance the detectability of pregabalin by forming a highly fluorescent dihydropyridine derivative. This process involves the condensation of pregabalin with acetylacetone and formaldehyde, yielding a yellowish-green compound measurable both colorimetrically at 338 nm and fluorimetrically at an emission wavelength of 486 nm (λexcitation = 408 nm). The reaction conditions were thoroughly optimized to obtain the highest possible sensitivity, reduce reagent and time consumption, and use safe solvents. The developed method displayed high sensitivity and linearity in the concentration ranges of 4.0 – 20.0 µg/mL in colorimetric assay and reached a nano-scale analysis level of 40 – 2000 ng/mL with a detection limit down to 10 ng/mL when adopting the fluorimetric measurement. Both assessments were rigorously evaluated for their performance, adhering to the International Conference on Harmonization (ICH) standards. The accuracy of these methods was confirmed through the recovery rates of real samples, showing 98.9 ± 0.2 % for colorimetric and 98.2 ± 0.7 % for fluorimetric assessment. The excellent sensitivity of the suggested spectrofluorometric approach led to its use in the measurement of PRG in spiked human urine samples, resulting in particularly good recoveries ranging from 95.3 to 102.8 %. Meanwhile, the Need, Quality, Sustainability (NQS) index looks into how necessary the method is, execution quality (evaluated using the RGB 12 algorithm), and how it fits with the Sustainable Development Goals (SDGs), underlining the benefits of employing natural reagents. The developed approach showed superiority in sensitivity and sustainability compared to previous analytical approaches for pregabalin.