Linear solvent strength model on porous graphitic carbon stationary phase using high temperature liquid chromatographic method for allopurinol related substances analysis

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 245; p. 116200
• Main Authors: Soós, Barnabás, Horváth, Krisztián, Kormány, Róbert
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.08.2024
• Subjects: Allopurinol; Allopurinol - analysis; Allopurinol - chemistry; Chromatography, High Pressure Liquid - methods; Drug Contamination - prevention & control; DryLab; Graphite - chemistry; High temperature liquid chromatography; Hot Temperature; Method development; Porosity; Porous graphitic carbon; Retention modeling; Solvents - chemistry; Temperature; Porous graphitic carbon; DryLab; Retention modeling; High temperature liquid chromatography; Method development; Allopurinol
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2024.116200

A high-performance liquid chromatography (HPLC) method was developed for the analysis of Allopurinol and its Ph.Eur. impurities using a porous graphitic carbon (PGC) stationary phase. Retention behavior of solutes was studied across a wide temperature range (30–90 °C) and various gradient times (5–20 min). Analysis of the data revealed distinct retention mechanisms between reversed-phase and PGC phases. However, it was proved that the retention of Allopurinol and its Ph.Eur. impurities on PGC stationary phase can be effectively modeled using the linear solvent strength (LSS) theory. This allows for the utilization of LSS-based method development software to optimize methods under these conditions. By using commercial chromatographic modeling software, separation of Allopurinol and Ph.Eur. impurities was optimized within a large design space. At the optimized operating conditions (pH = 2.0, tG = 6 min, T = 60 °C), all solutes were separated within 6 min with baseline resolution. Comparison between predicted and experimentally measured chromatograms further confirmed the applicability of LSS theory in developing analytical methods for PGC-based HPLC systems. The presented approach offers a general framework for method development on PGC phases. •Allopurinol and its Ph.Eur. impurities are analyzed with porous graphitic carbon.•The retention behavior is different than in reversed phase separations.•Linear solvent strength (LSS) theory can be used for method development.•All compounds can be separated in 6 min with baseline resolution.•LSS-based method development software are efficient for PGC phases.