Consumption of the Sugar Substitute Stevia Leads to Cross-Reactivity of CEDIA(R) Buprenorphine II Immunoassay

Consumption of the Sugar Substitute Stevia Leads to Cross-Reactivity of CEDIA(R) Buprenorphine II Immunoassay


Plattner,S.; Pavlic,M.; Pitterl,F.; Schubert,B.;

Buprenorphine is a semisynthetic opioid that is often used in opiate maintenance therapy. For this purpose, regular toxicological analyses of urine samples are mandatory. For fast analytical results, analyses are commonly performed by immunoassay, for example, Thermo Scientific CEDIA(R) Buprenorphine or Buprenorphine II assay. One drawback of immunoassay-based methods is the possible cross-reaction with other substances. Several drugs have already been checked for cross-reactivity to CEDIA(R) Buprenorphine II immunoassay. In contrast, cross-reactivities have not been checked for any food additives. In the present study, a cross-reaction of CEDIA(R) Buprenorphine II assay to steviol glucuronide was investigated. Steviol glucuronide is a phase II metabolite of the sugar substitute stevia. For our study, 32 urine samples of patients in rehabilitation centers were collected. These samples were tested positive with the CEDIA(R) Buprenorphine II immunoassay. These findings were suspicious, because it was highly unlikely that the patients in those institutions had access to buprenorphine. The absence or presence of buprenorphine in urine samples was evaluated by a validated gas chromatography-mass spectrometry method. In order to determine the concentration of steviol glucuronide in urine samples, a liquid chromatography-tandem mass spectrometry method has been developed and fully validated according to the respective guidelines of the German Society of Toxicological and Forensic Chemistry. The cross-reactivity of steviol glucuronide in the CEDIA(R) Buprenorphine II immunoassay was observed at concentrations above 15,000 microg/L. These findings demonstrate that food additives should also be considered as compounds that may reduce the selectivity of immunoassays and emphasize the importance of confirming implausible results by selective analytical methods.

J Anal Toxicol 2021 45:1052-1057
PubMed: 33104778