UPLC‐MS/MS‐Based Analysis of the Impact of Polypharmacy on Quetiapine Plasma Concentrations

Quetiapine, a second-generation atypical antipsychotic, has broad indications and considerable variation in daily prescribed doses across different diseases, yet its therapeutic window remains narrow (100-500 ng/mL). In clinical practice, quetiapine is frequently co-administered with other psychotropic drugs. To evaluate the impact of commonly co-administered medications on quetiapine plasma concentrations, we developed and validated a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of quetiapine and 16 commonly co-administered psychotropic drugs in human plasma. Method validation demonstrated good linearity for all analytes, with precision (CV < 15%), accuracy (85%-115%), and extraction recovery (85%-115%) meeting acceptance criteria. Matrix effects were negligible, and no significant carryover or interference was observed. Results revealed complex polypharmacy regimens within the cohort, with up to six psychotropic drugs co-administered with quetiapine. Among the 16 subjects, 56.2% exhibited subtherapeutic quetiapine concentrations (< 100 ng/mL), more frequent in patients co-administered with alprazolam or mirtazapine. It is therefore speculated that alprazolam, mirtazapine, and related agents may influence quetiapine systemic exposure. Clinically, when co-administered with these agents, quetiapine plasma concentrations should be monitored regularly to ensure efficacy and safety.