Paper spray mass spectrometry: A new drug checking tool for harm reduction in the opioid overdose crisis.

Fentanyl and related psychoactive substances are at the forefront of the opioid overdose crisis, for which a complete solution is not immediately obvious. Drug testing for harm reduction may be an effective approach to both reduce overdoses and importantly, engage people who use drugs (PWUD) with the medical system. Paper spray mass spectrometry (PS-MS) is an ambient ionization strategy that is uniquely suited to address this complicated analytical task. This perspectives article presents the merits of PS-MS, with a focus upon the current state of its use as a candidate drug checking strategy for harm reduction. PS-MS is inherently sensitive and selective, with detection limits in the picogram range. It requires small drug samples (~1 mg) for quantitative drug testing, critical to encourage pre-consumption measurements by PWUD in the context of a harm reduction strategy. Calibrations obtained in surrogate drug matrices containing highly concentrated primary drugs demonstrate comparable sensitivities, a wide calibration range, and minimal matrix effects. PS-MS can be interfaced with high-resolution MS for non-targeted analysis, allowing the identification of novel psychoactive substances as they appear in street drugs. Individual quantitative PS-MS measurements for drug testing can be done in 1 minute or less, resulting in high sample throughput. Significant advancement in mass spectrometer miniaturization and mobilization has concomitant benefits for direct, on-site drug checking, such as reduced cost, simplified maintenance and ease of use by less skilled operators. While PS-MS technology continues to rapidly advance, it is our opinion that PS-MS can be utilized as an effective tool for harm reduction in the opioid overdose crisis.