High-resolution two-dimensional liquid chromatography analysis of key linker drug intermediate used in antibody drug conjugates

Recent Advances in Chromatography for Pharmaceutical Analysis

“…In this context, several practical charts have been proposed to discover the most suitable analytical method. [229][230][231] Based on the volatility of the PGIs/GIs/MIs, the selection of its analytical technique can lead to either gas chromatography (GC) or liquid chromatography (LC) analysis, whereas the choice of the detector is defined based on the required limits the impurity must meet while avoiding matrix effects.…”

“…2D-GC approaches can be applied as a last resort when all of the abovementioned techniques were unsuccessful in terms of selectivity. 229,230 As For non-volatile PGIs/GIs, RPLC is generally applied as the first choice coupled to either UV or MS detection depending on the chromophoric properties of the impurity. Then, other modes of chromatography might be selected for polar or ionizable compounds, namely HILIC and mixed-mode chromatography (MMC).…”

“…Finally, 2D-LC(-MS) can be helpful when all of the other approaches do not meet the required selectivity and sensitivity. 229,230 A comprehensive example of method development for PGI identification and characterization was recently published by Huang et al 233…”

“…139 HIC × RPLC-HRMS was performed by Sarrut et al 139 Recently, the thorough and simultaneous characterization of both small and large molecules (drug payloads decorating mAbs in ADC formats) has also stimulated interest in the applications of 2D-LC. 136,137,139 As practical examples, Venkatramani et al 141 coworkers, 144 by analyzing several commercial mAbs and ADCs. It was found that the UHP-SEC columns were equivalent in terms of mAb characterization performance, since the average resolution for each column was between 1.9 -2.1 for the monomer and dimer forms of 10 different commercial mAbs.…”

“…Trace analysis of Mutagenic impurities is one area where 2D-GC has been successfully applied owing to the improved selectivity (see section 11). 229,230,264 Metabolomics is another area where it has been utilised to support drug discovery and development. Several groups are developing new technologies and strategies for the definition of the composition of volatile and non-volatile biologically active secondary metabolites of plants and plant products of interest in the pharmaceutical sectors.…”