Determination of naloxone and its impurities in a vaporized matrix by LC-MS/MS: Application of an in vitro surrogate model platform to assess in vivo permeation and risk associated with vaping opioids.

E-cigarette use in the U.S. has risen over the past decade, particularly among youth and young adults, prompting potential public health concerns. In response, public health agencies including the FDA have initiated studies to assess associated risks from vaping. This work describes our efforts to develop novel in vitro test procedures to help understand the potential for vaped drug products to permeate lung tissue. Using naloxone as a model drug, we validated an LC-MS/MS method according to the ICH M10 bioanalytical guidance. This method was then applied to measure naloxone and its impurities in cell culture medium after exposure to vaped aerosols. The exposure was simulated using a VC-1 smoking machine (VitroCell®) and human bronchial epithelial cells. This newly established platform for examining vaped naloxone exposure provides a means to examine vaped drugs of abuse or misuse with the ultimate goal being to mitigate risk to young adults.