Spatiotemporal Mapping of Drug Incorporation in Human Nails by MALDI-FTICR-MSI

Keratinized matrices, such as hair, are used in forensic toxicology as an alternative sample for a retrospective view of drug use. However, the analysis requires extensive sample preparation and analysis using chromatographic techniques, such as LC-MS. While this method is sensitive, it requires a large amount of sample, often uses established panels for targeted analysis, and provides data on a monthly basis. MALDI-MSI has previously been used to monitor the distribution of drugs and metabolites in hair samples, providing more accurate, visual, and chronological data. However, other keratinized matrices, such as nails, are also gaining interest in the forensic community, as they can incorporate drugs as the nails grow. Additionally, nails have a slower growth rate (1-3 mm/month, depending on the nail location), making them better suited for detecting lower concentrations of circulating compounds or for long-term monitoring. In this study, thin sections of full nails obtained from postmortem subjects and clippings from volunteers undergoing prolonged medication use were prepared for analysis by MALDI-FTICR-MSI. By analyzing the samples in an untargeted manner, the simultaneous detection of multiple medications, metabolites, and endogenous species could be achieved. Using the average nail growth rate and the pixel size, a more accurate time frame for drug incorporation can be determined. The work presented here demonstrates the application of MALDI-MSI to monitoring the distribution of drugs in nail samples and could provide complementary information to forensic investigations.