Document Type

Article

Publication Date

8-20-2025

Publication Title

The Journal of Applied Laboratory Medicine

Department

Geisel School of Medicine

Abstract

Background

Loperamide is a µ-opioid receptor agonist that reduces intestinal peristalsis and is used to treat diarrhea. We previously described significant cross-reactivity of loperamide with 2 fentanyl immunoassays. Since then, new fentanyl immunoassays, including a CLIA-waived point-of-care device, have been approved for clinical use. Methods

We evaluated new fentanyl immunoassays for cross-reactivity to loperamide and its major metabolites, N-desmethyl loperamide (dLop) and N-didesmethyl loperamide (ddLop). Previously characterized assays were tested for cross-reactivity to ddLop, which recently became commercially available. Loperamide, dLop, and ddLop were spiked in drug-free urine for analysis by 5 enzyme immunoassays run on automated chemistry analyzers and one lateral flow assay for the detection of fentanyl. Results

Loperamide and its metabolites produced positive results in 3 fentanyl immunoassays. The Immunalysis HEIA was previously determined to be reactive to both loperamide and dLop, but it was not reactive to ddLop. The Immunalysis SEFRIA was reactive to loperamide, dLop, and ddLop at minimum concentrations of 14.7 mg/L, 13.1 mg/L, and 17.0 mg/L. The Thermo Fisher DRI was previously determined to be reactive to loperamide and dLop, and it was reactive to ddLop at a minimum concentration of 33.1 mg/L. The Abbott iCassette, ARK Fentanyl II, and Lin-Zhi LZI II fentanyl assays showed no cross-reactivity to loperamide or its metabolites. Conclusions

The cross-reactivity of loperamide, dLop, and ddLop in several fentanyl immunoassays has the potential to cause false-positive results during urine drug screening.

DOI

https://doi-org.dartmouth.idm.oclc.org/10.1093/jalm/jfaf110

Original Citation

Michael E Walsh, Grace R Williams, Paul J Jannetto, K Aaron Geno, Evaluating Updated Fentanyl Immunoassays for Loperamide Interference, The Journal of Applied Laboratory Medicine, Volume 10, Issue 6, November 2025, Pages 1607–1613.

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