Underreporting of synthetic cathinone poisoning with clinical immunoassays: An experimental and observational study (2025)

Background: There is an increasing global concern about the use of synthetic cathinones (SCs). Detecting these drugs in human urine samples can be difficult, particularly in emergency settings. Cross-reactivity has been described for several immunoassays. We evaluated the analytical interference caused by common SCs in MDMA and amphetamine assays that use the EMIT® Atellica CH (Siemens Healthineers) with both clinical and in vitro experimental data.
Methods: Drug-free urine samples were spiked with various concentrations (5 to 100 µg/mL) of 2-methylmethcathinone (MMC), 3-MMC, 4-MMC, 3-chloromethcathinone (CMC), methylone and alpha-PHP and tested using EMIT® assays. The percentage of false-positive results was determined in urine samples from patients above 18 years of age admitted to the ICU or emergency department who underwent routine toxicology screening and urine immunoassays over a 4-year period. Confirmatory analyses of SC were performed by mass spectrometry techniques.
Results: False-positive results occurred for the MDMA assay with methylone (10 µg/mL) and 3-CMC (100 µg/mL) and for the amphetamine test with 2-MMC (50 µg/mL). We studied 2033 urine samples from 1812 patients (mean age 39 years, 61.8% male), of which 49 tested positive for amphetamine and 76 for MDMA. SCs were responsible for a false-positive rate of 16.3% for the amphetamine tests and 17.1% for the MDMA tests. Most of the false-positive tests occurred among young male patients (mean age 38 years, 92.8% male).
Conclusions: This study demonstrates that SC intoxication may be underreported in immunoassay toxicology testing. Due to a lack of specificity of screening immunoassay methods, positive results for amphetamine-type stimulants should be confirmed by specific MS methods. [Author's abstract]