Therapeutic drug monitoring using LA-ICP-MS: Initial studies with metallodrugs in mouse whiskers

As modern drugs become increasingly potent and specific, therapeutic drug monitoring (TDM) becomes ever more important. Theoretically, hair is the best tissue to sample for TDM because it can be sampled noninvasively, any time, and records body chemistry over time. In practice, it is not being used for lack of a good analytical technique. In this study we demonstrate that LA-ICP-MS profiling can be used to trace both deposition and elimination of three metallodrugs in mouse whiskers. Two gadolinium-based and one vanadium-based complexes were administered to ICR mice. After optimization of ablation modes and laser conditions, LA-ICP-MS profiling was performed by line scan with laser spot size of 100 μm along the whiskers of the mice. For gadolinium complexes, gadodiamide and gadoteric acid, different deposition behaviors were recorded, including degree of deposition as a function of dosage levels. Furthermore, the deposition of Gd for high dose (0.1 mmol/kg) was found to be three times that for low dose (0.01 mmol/kg). For the vanadium complex, vanadyl acetylacetonate, asymmetric peaks were observed in the whiskers' profiles at around 1400 and 1900 μm from the follicle, giving valuable information about the absorption/elimination of the drug, and by extension, its metabolism. To the best of our knowledge, this is the first example of LA-ICP-MS bioimaging being used to record the deposition of metallodrugs administered in different dosages. Our results suggest LA-ICP-MS has enormous potential for application in the field of therapeutic drug biomonitoring, particularly using hair for sampling purposes.