Underutilization of fentanyl testing masks substantial fentanyl exposure in routine urine drug screens in Indiana

Timely and locally relevant drug testing is helpful for overdose assessment; however, immunoassay (IA)-based urine drug screens (UDS) often fail to detect emerging substances. This study assesses fentanyl screen utilization and positivity rate, concurrent xylazine presence in fentanyl positive specimens, and compares this information with the fentanyl overdose data from the Indiana Department of Health.

Consecutive urine specimens (n = 2052) submitted for UDS were screened by fentanyl immunoassays (total, n = 1864; n = 188 had insufficient volume). Presumptive positive specimens were analyzed by LC-MS/MS for fentanyl, norfentanyl, 4-anilino-N-phenethylpiperidine (4-ANPP), and xylazine. Based on ZIP code information, fentanyl presumptive positive data was correlated with state overdose data.

Of the specimens submitted for UDS, 1.6% (n = 33) included a fentanyl order. IA screening of the remainder resulted in 13% (n = 233) presumptive positivity, of which 97% (n = 226) confirmed positive. Xylazine was also detected in 48 specimens. Fentanyl screen positive specimens originated from areas with higher overdose deaths.

IAs remain central to UDS but available panels often lag behind emerging drug trends. As fentanyl drives rising overdose rates, rapid detection is critical. This study highlights increased fentanyl detection in a clinical UDS cohort across Indiana and emphasizes that UDS negative results may not indicate drug-free specimens, therefore, UDS panels should be updated based on emerging trends and assay availability.