First Specific Analytical Method for Quantification of Halide Ions by UHPLC-MS Using Reverse Phase Chromatography C18

In the pharmaceutical industry, optimizing methods for trace detection and stoichiometry determination of salts is highly sought after, particularly for studies on pharmaceutical compounds in the development phase. Current methods for halide ion detection are commonly carried out using ion chromatography (IC) due to the high specificity and sensitivity of this technique, which allows the detection of various ions at very low concentrations. Advanced techniques such as mass spectrometry, which offers significantly higher sensitivity thanks to its specificity, can be particularly advantageous in analytical applications both for trace detection with a view to quantification and for its accuracy in stoichiometric calculations, allowing the precise determination of the ratio between the compound of interest and the counterion. To our knowledge, no LC-MS methods using a reverse-phase polarity chromatographic system (C18), commonly employed in high-performance liquid chromatography (HPLC) or ultrahigh-performance liquid chromatography (UHPLC), currently exist that allow for sufficiently effective halogen separation for accurate quantification. We present a new rapid and efficient method compliant with International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use standards using a C18 reverse phase, which enables optimal separation of three halogens in order to precisely quantify analytes through mass spectrometry. This method will be illustrated with a relevant application, dedicated to the stoichiometry investigation of pharmaceutical compounds in the form of salts or halide ion residues.