Norbuprenorphine Interferences in Urine Drug Testing LC–MS-MS Confirmation Methods from Quetiapine Metabolites

Norbuprenorphine interferences were observed in urine drug testing LC–MS-MS confirmation methods used to assess patient compliance with prescribed buprenorphine for chronic pain and opioid use disorder. The interferences were observed in the norbuprenorphine MS-MS transitions, m/z 414.4/83.1 and 414.4/187.2, at and near the norbuprenorphine retention time at multiple laboratories using different sample preparation procedures and chromatographic conditions. When the interferences were present, a norbuprenorphine result could not be reported. Upon investigation, the interferences were correlated with prescribed quetiapine (Seroquel, Seroquel XR), a second-generation antipsychotic medication approved for the treatment of schizophrenia, bipolar disorder and more recently as an adjunct treatment for major depressive disorder. In addition to the approved indications, quetiapine is prescribed off-label for other conditions including insomnia and anxiety disorders. Off-label prescribing has increased in recent years, thereby exacerbating this analytical issue. Here, we present the study of four quetiapine metabolites found to have significant direct or potential interferences in norbuprenorphine quantitation. The four metabolites were putatively identified as two hydroxyquetiapine acids differing in the site of hydroxylation and a quetiapine sulfoxide acid diastereomer pair. As a result of this study, interference-free norbuprenorphine MS-MS transitions, m/z 414.4/340.2 and 414.4/326.1, were found that were selective for norbuprenorphine while maintaining an acceptable 10 ng/mL lower limit of quantitation.