Development and Application of the Modular MasSpec Pen System for Clinical Opioid Screening

Mass spectrometry (MS) is an important tool for opioid screening due to the high analytical sensitivity and chemical specificity provided by MS for small molecule analysis. MS techniques that can provide direct detection of opioids are of high interest to simplify and expedite patient screening workflows. Here, we describe the development and application of the MasSpec Pen (MSPen) technology as a modular system for opioid screening in which sampling and MS analysis are decoupled. With the modular MSPen system, the rapid, direct, and non-destructive nature of sample collection provided by the MSPen device are retained, followed by analysis using a MS method suitable for the intended use. We used the modular MSPen system and electrospray ionization MS to detect oxycodone, hydrocodone, fentanyl, hydromorphone, and morphine both individually and as mixtures. Detection and quantification limits in the single nanogram range were achieved when analyzing standards deposited on surfaces as well as ex vivo human skin doped with opioids. We then tested the feasibility of the modular MSPen system at the Johns Hopkins Bayview Medical Center to analyze opioids from direct sampling of patient skin, compared to results obtained from the patients' urine and saliva. Altogether, the modular MSPen system allowed direct sampling and semi-quantitation of opioids from surfaces and patients' skin, with the opportunity to be further developed for other screening applications.