Ambient Laser Desorption Low-Pressure Dopant-Assisted Photoionization Mass Spectrometry for Detection of Nicotine and Caffeine in Single Human Hair.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) allows spatial mapping of drug molecules within single hair samples, demonstrating significant potential as a tool for verifying drug abuse and assessing medication adherence. However, the technique still suffers from reliance on matrix-assisted molecules and issues of ionization suppression. In this work, a matrix-free ambient-pressure laser desorption low-pressure dopant-assisted photoionization (LD-LP-DAPI) source was developed. It retains the operational convenience of ambient-pressure ionization while effectively eliminating ion suppression through low-pressure postionization. To compensate for the loss of sensitivity caused by sample dilution under low-pressure conditions, acetone-assisted photoionization was adopted in an ion funnel, enhancing the ionization efficiency by 2 orders of magnitude. The method successfully mapped the spatial distribution of nicotine and caffeine in soaked hair samples, achieving a spatial resolution of 102 μm, and yielded signal-to-noise ratios (S/N) of 572 for nicotine (at 50 μg/mL) and 94 for caffeine (at 20 μg/mL). Furthermore, cigarette exposure experiments ranging from 0 to 120 min were performed to obtain the relationship between nicotine deposition on hair surfaces and exposure time. These results demonstrate the considerable potential of this novel ionization source for rapid monitoring of drug molecules in hair samples, offering a powerful tool for forensic toxicology and related applications.