LAUSR

To the Editor: We previously reported on an alternative activity-based screening method to detect (synthetic) opioids/opiates in blood samples (1) in which μ-opioid receptor activation could be monitored via a split-luciferase system. The ability for the opioid signal to be detected from “baseline” is a combination of the receptor activation capability and the concentration of the drug in the sample. A strongly receptor-activating drug at low concentrations could give the same signal as a weaker activating drug at a higher concentration. For hydromorphone, a concentration of 0.285 ng/mL (38.5 pg in well) could be detected, whereas for a strong opioid like carfentanil, a concentration as low as 0.79 pg/mL (0.11 pg in well) could be picked up. Taking into account the concentrating and dilution steps throughout the sample preparation, these correspond to theoretical blood concentrations of 0.385 ng/mL and 1.07 pg/mL, respectively (1). Our “untargeted” screening approach has 1 major limitation: because it is based on the biological activity of the (synthetic) opioids, the co-occurrence of opioid antagonists (e.g., naloxone/naltrexone) is an important restriction. These antagonists not only serve as antidotes in vivo in (suspected) overdose cases but also prevent the in vitro opioid receptor activation in our bioassay, resulting in false negatives. Although naloxone was …