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.