Cross-Reactivity of Tapentadol Specimens with DRI Methadone Enzyme Immunoassay

Abstract

A substantial incidence of positive methadone screens for pain management urine specimens using a commercial enzyme immunoassay (EIA) was observed in the absence of a methadone prescription, with negative methadone confirmation by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS). Tapentadol was the only common prescription among the investigated specimens. Tapentadol or one of its three major metabolites was tested at various concentrations (100-200,000 ng/mL) against the DRI EIAs for methadone and methadone metabolite, to evaluate cross-reactivity. Ninety-seven authentic tapentadol urine specimens that produced false-positive methadone EIA results (cutoff = 130 ng/mL) were analyzed for methadone and tapentadol in compound-specific UPLC-MS-MS confirmation tests. Tapentadol, tapentadol glucuronide, tapentadol sulfate and N-desmethyltapentadol exhibited cross-reactivity with the methadone EIA at 6,500 (2.2%), 25,000 (0.6%), 3,000 (4.4%) and 20,000 ng/mL (0.9%), respectively. No cross-reactivity was observed with the methadone metabolite 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine EIA. All authentic urine specimens were confirmed to be negative for methadone, but positive for tapentadol and all monitored metabolites. Individual concentrations indicated that separate or combined urinary concentrations of tapentadol and its conjugates may produce false-positive methadone screens through cross-reactivity with the methadone immunoassay. The potential for false-positive results for methadone EIA screening of urine specimens associated with tapentadol prescriptions should be considered when interpreting results.

What Can a Urine Drug Screening Immunoassay Really Tell Us?

“…Poppy seed containing foods 1,2,18,48 , some fluoroquinolone antibiotics (levofloxacin 49 , ofloxacin 49 ), imipramine 46 , naltrexone 46 , naloxone 50 , rifampin/rifampicin 51 53 , verapamil 54 , verapamil metabolites 54 , quetiapine 55,56 , tapentadol 57 None known-methadone-specific immunoassays have adequate sensitivity to detect methadone and/or EDDP in urine Buprenorphine Common targets Buprenorphine Norbuprenorphine (met)…”

Laboratory Testing for Prescription Opioids

“…Methadone-specific analysis techniques are therefore required for its detection, and immunoassays such as the DRI methadone assay (Microgenics Corp, Freemont, CA, USA) are commercially available for this opioid drug. Recently, tapentadol, a newer prescription analgesic, has been shown to react with the DRI methadone assay producing false positive results [73]. Although the cross-reactivity in the assay is low, it illustrates the need for confirmatory testing especially when the result does not fit with the clinical situation.…”

Can tapentadol cause a false-positive urine drug screen result for amphetamine?

“…Although we found no amphetamine cross-reaction with the immunoassay, another recent study has demonstrated cross-reactivity with a similar immunoassay for methadone. 7 …”