Advances in fentanyl testing.

Fentanyl is a synthetic opioid that was approved by the FDA in the late 1960s. In the decades since, non-prescription use of fentanyl, its analogs, and structurally unrelated novel synthetic opioids (NSO) has become a worsening public health crisis. There is a clear need for accessible testing for these substances in biological specimens and in apprehended drugs. Immunoassays for fentanyl in urine are available but their performance is restricted to facilities that hold moderate complexity laboratory licenses. Immunoassays for other matrices such as oral fluid (OF), blood, and meconium have been developed but are not widely available. Point of care tests (POCT), such as lateral flow immunoassays or fentanyl test strips (FTS), are widely available but not approved by the FDA for clinical use. All immunoassays are vulnerable to false positive and false negative results. Immunoassays may or may not be able to detect fentanyl analogs and NSOs. Mass spectrometry (MS) can accurately and reliably measure fentanyl and its major metabolite norfentanyl in urine and oral fluid. MS is available at reference laboratories and large hospitals. Liquid chromatography paired with tandem mass spectrometry (LC-MS/MS) is the most widely used method and has outstanding specificity and sensitivity for fentanyl and norfentanyl. When compared to immunoassays, MS is more expensive, requires more technical skill, and takes longer to result. Newer mass spectrometry methods can measure fentanyl analogs and NSO. Both mass spectrometry assays and immunoassays [in the form of fentanyl test strips (FTS)] have potential use in harm reduction programs.