This investigation examines the feasibility of detecting changes in intact human hair upon drug exposure using diamond attenuated total reflection (ATR) infrared spectroscopy. Prior work on microtomed hair has reported spectra changes in the medulla of the hair resulting from drug exposure. This study focuses on examining the hair <i>intact</i>, eliminating sample preparation and thereby reducing the possibility of sample contamination. Several hair samples were first examined to determine whether the lipids in the medulla could be detected from intact hair. Once this was established, hair samples exposed to drugs were investigated to see if changes in those lipids could be detected. Both internal and external drug exposures were investigated: hair samples were externally (incorporated) exposed to Clozapine and real-life samples were obtained from a patient on alprazolam (Xanax<sup>™</sup>). In both cases, spectral differences in the C–H bands were observed in the hairs with drug exposure as compared to hair with no known drug exposure. These changes are consistent with changes in the lipids in the medulla.
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