Chromatographic retention and ionization behavior of azole-containing drugs: a comparative study from classical to green analytical chemistry

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Başat Dereli D., Çubuk Demiralay E., Daldal Y. D.

NEW JOURNAL OF CHEMISTRY, cilt.1, ss.1-15, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1039/d6nj02728h
  • Dergi Adı: NEW JOURNAL OF CHEMISTRY
  • Derginin Tarandığı İndeksler: Academic Search Ultimate (EBSCO), Scopus, Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest), Science Citation Index Expanded (SCI-EXPANDED), Chemical Abstracts Core, Chimica, Compendex, EMBASE, DIALNET
  • Sayfa Sayıları: ss.1-15
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Süleyman Demirel Üniversitesi Adresli: Evet

Özet

This study determined both the retention behavior and dissociation constant (pKa) values of azole-group-containing compounds, which represent unique skeletal structures in pharmaceutical chemistry, as a function of pH change, which are important for method optimization using an environmentally friendly method. To characterize the retention, ionization, and ADME profiles of sertaconazole, clotrimazole, climbazole, oxiconazole, thiabendazole, albendazole, mebendazole, and metronidazole, reversed-phase liquid chromatography (RPLC) analysis was performed using acetonitrile (ACN), methanol (MeOH), and ethanol (EtOH), a non-toxic green alternative, in the hydroorganic mobile phase. Chromatographic retention data were systematically obtained at 37 °C using a Zorbax SB-CN column over a wide range of mobile phase pH values and organic modifier concentrations. pKa (sspKa) values in the water–organic solvent binary mixture were calculated using complementary nonlinear regression (NLREG) and linear dissolution energy relationship (LSER) modeling, showing excellent fit. Using these values, the pKa (wwpKa) values of the compounds in aqueous medium were calculated using Yasuda–Shedlovsky and mole fraction approximations. A comprehensive ADME profile was determined using the experimental hydrophobicity descriptor (φ0), molecular weight, and topological polar surface area (TPSA). Thus, the experimental chromatographic data demonstrated that in silico methods can overcome their limitations. Finally, the environmental sustainability and applicability of the developed methods were quantitatively validated using AGREE, MoGAPI, AGSA, BAGI, and CACI metrics, proving that the green EtOH–water system provides a highly sustainable (AGSA score: 86.11), practical (BAGI score: 80), and fast (CACI score: 77) analytical platform.