Determination of fosfomycin trometamol and its related substances in the bulk drug by ion-pair HPLC with evaporative light scattering detection

摘要

Ion-pair high performance liquid chromatography (HPLC) with an evaporative light scattering detector was used to develop a method for the determination of fosfomycin trometamol and its related substances in the bulk drug. Utilizing a Luna 5 mu m C-18 column at 35 degrees C, evaporation temperature of 45 degrees C, and nebulizing gas pressure of 3.5 bar, the optimized mobile phase was a 15 mM octylamine solution (adjusted to pH 5.2 with glacial acetic acid) with acetonitrile (92 : 8), and the flow rate was maintained at 1.5 mL/min. Validation of the method was performed, and specificity, reproducibility, precision, and accuracy were confirmed. The linear range for fosfomycin trometamol and fosfomycin trometamol impurity A was 48.7-292 mu g/mL and 10.5-84 mu g/mL, respectively. The limit of quantitation was 16.3 mu g/mL for fosfomycin trometamol and 10.7 mu g/mL for fosfomycin trometamol impurity A. Due to its simplicity and accuracy, this method is particularly suitable for routine quality control of fosfomycin trometamol, and can probably be applied to the determination of fosfomycin and related substances in fosfomycin sodium and fosfomycin calcium.