Negative-Ion ICP-MS as a Novel Strategy for Fluorine and Bromine Determination in Pharmaceutical Research

Objective

Halogens occur in about 25 percent of approved small-molecule drugs and are key tracers in ADME studies, yet quantitative metabolite profiling still depends on radiolabeled compounds that are costly to synthesize and generate radioactive waste. This project will pioneer negative-ion ICP-MS for pharmaceutical halogen analysis, offering a radiolabel-free, structure-independent alternative that enables direct, sensitive detection of fluorine or bromine. The objectives are to: (1) establish validated methods for bulk quantification of F and Br in biological matrices; (2) develop HPLC–negative-ion ICP-MS for robust and quantitative metabolite profiling; and (3) deliver quantitative two-dimensional maps revealing the distribution of halogenated drugs in tissues at micrometer-size resolution via LA-ICP-MS using matrix-matched standards. The work will implement and optimize a pre-commercial prototype, characterize reagent backgrounds and spectral interferences, mitigate them using collision–reaction cell technology, and determine figures of merit—reporting limits of detection in absolute units (mass per sample for bulk ICP-MS, on-column mass for HPLC–ICP-MS, and areal LoD for LA-ICP-MS), with ng per g equivalents where appropriate—before applying the workflows to pharmaceutical samples with input from industry; performance targets will be refined after pilot tests in relevant matrices. Results will advance plasma spectrometry at bulk, molecular, and spatial levels, reduce reliance on radiotracers and the use of animals, and deliver the an end-to-end, radiolabel-free workflow for halogen quantification across bulk analysis, chemical speciation, and elemental mapping.