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An Opioid Hiding in Plain Sight: Loperamide-Induced False-Positive Fentanyl and Buprenorphine Immunoassay Results. J Appl Lab Med 2022 Oct 29;7(6):1318-1328

Date

08/30/2022

Pubmed ID

36036092

DOI

10.1093/jalm/jfac065

Scopus ID

2-s2.0-85141005657 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

BACKGROUND: Loperamide (Imodium®), a commonly used anti-diarrheal, is a mu opioid receptor agonist that, like all opioids, reduces gastrointestinal tract peristalsis. Loperamide is considered to have low abuse potential as it does not produce an analgesic or euphoric effect due to low bioavailability and first-pass metabolism. However, reports of individuals misusing loperamide through the use of super-therapeutic doses, alone or in combination with P-glycoprotein and/or CYP450 enzyme inhibitors, is increasing. We hypothesized that loperamide could potentially cross-react with laboratory immunoassay drug screens.

METHODS: Drug-free urine was spiked with loperamide or its principal metabolite, N-desmethyl loperamide (dLop), and assayed on multiple fentanyl and buprenorphine assays. Fentanyl immunoassay screen-positive results at one institution were examined by high-resolution mass spectrometry (MS) for the presence of loperamide and quantified by liquid chromatography- tandem MS when positive.

RESULTS: Loperamide produced positive results on the Thermo DRI Fentanyl and Immunalysis Fentanyl assays at concentrations greater than 5.72 mg/L and 23.7 mg/L. dLop generated positive results for the Thermo DRI and Immunalysis fentanyl assays at concentrations exceeding 6.9 mg/L and 35.7 mg/L. dLop also produced positive buprenorphine results on the Thermo CEDIA buprenorphine assay at concentrations exceeding 12.2 mg/L. High-resolution MS analysis of 225 fentanyl immunoassay positives (Thermo DRI) yielded 5 specimens containing loperamide and/or dLop, 4 of which contained measurable quantities of fentanyl in addition to loperamide/dLop.

CONCLUSIONS: Laboratories using these assays should be aware of the potential for false-positive screening results due to the presence of high concentrations of loperamide and its metabolite dLop.

Author List

Geno KA, Badea A, Lynch KL, Jannetto P, Hubbard JA, Nerenz RD, Cervinski MA

Author

Robert D. Nerenz PhD Associate Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Buprenorphine
Fentanyl
Humans
Immunoassay
Loperamide