Assessment of Seven Process Associated Solvent Impurities and two by-Product Associated Solvent Impurities in Ibandronate Sodium Bulk Material and Commercial Product Employing Gas Chromatography

Abstract

A gas chromatography technique coupled with head space sampling and detection with flame ionizer approach (GST-HSS-FI) methodology was established to determine seven process associated solvent impurities (acetone, ethyl acetate, methanol, mesityl oxide, chlorobenzene, diacetone alcohol, isopropyl alcohol) and two by-product associated solvent impurities (ethyl vinyl ketone and methyl isobutyl ketone) in ibandronate sodium bulk material and ibandronate sodium commercial product. By using dimethyl sulphoxide and clean water (70%:30% v/v) as a solvent, the standard curves for target solvent impurities with correlation coefficient scores over 0.99 were effectively plotted by GST-HSS-FI methodology in a selected concentration range (LOQ measure level to 120% of acceptable limit level). The approach was used to the identification of volatile target solvent impurities in ibandronate sodium bulk material and commercial product to validate its realistic application capacity. The GST-HSS-FI methodology presented the good, precise, accurate, specific and robust detection and assessment of volatile target solvent impurities, demonstrating its aptness to characterise the quality profile of ibandronate sodium bulk material and ibandronate sodium commercial product.