Developing a solid-phase extraction method based on a novel polymer-silica composite for analysis of sulfonate genotoxic impurities in drugs

Abstract

Genotoxic impurities (GTIs), which are present at very small amounts in drugs, can cause severe toxicity. The existence of GTIs poses a significant risk to patients, pharmaceutical companies, and regulatory agencies. Sulfonate compounds, as a typical genotoxic impurity, present a challenge in quantitative analysis because of their low concentration and instability. In this work, by a green, simple and low-cost preparation strategy, a novel polymer was modified on the surface of silica by the reaction of two monomers (1,5-dihydroxynaphthalene and 1,3,5-trimethylhexahydro-1,3,5-triazine). By systematically optimizing the ratio and concentration between the two polymeric monomers and silica, the resultant adsorbent labeled as S-D₁T₁/20 was obtained and showed outstanding adsorption performance for sulfonate. Mechanism studies revealed that there are effective hydrogen bond and π-π stacking interactions between S-D₁T₁/20 and sulfonate. For the partial sulfonates which are easy to hydrolyze, we proposed to detect the concentration of their hydrolyzed forms. By optimizing the loading and eluting conditions, an SPE-HPLC-DAD method with high sensitivity was developed for the quantitative enrichment and determination of six sulfonates with a wide linear range (0.01 ∼ 3μg mL⁻¹), low limits of detection (5 ∼ 25 ng mL⁻¹), satisfied inter-day precision, and intra-day precision. Last, this method was successfully applied to various species and forms of commercial drugs and achieved satisfied sulfonate recoveries (91.2 % ∼ 105.8 %). This work provides a unique solution to the frontier scientific problem of accurate determination of trace sulfonate genotoxic impurities in drugs, which is of great significance for ensuring drug quality and clinical safety.