Rapid On-Demand Point-of-Care Monitoring of Clozapine and Its Metabolite Norclozapine Using Miniature Mass Spectrometry

Clozapine remains the gold standard for treatment-resistant schizophrenia. However, its narrow therapeutic window and risk of severe side effects require close monitoring of both clozapine and its primary metabolite, norclozapine. Existing therapeutic drug monitoring (TDM) methods are limited by delays, high costs, and operational complexity. This study introduces three rapid point-of-care (POC) assays utilizing a miniature mass spectrometer (Mini-MS) to quantify clozapine and norclozapine in plasma, whole blood, and dried blood spots (DBSs), facilitating applications across diverse clinical settings.

The Mini-MS assay accurately quantified both analytes within therapeutic ranges across all Matrices.Results from the Mini-MS analysis showed excellent correlations with LC-MS/MS results (r = 0.998).In this proof-of-concept study, the Mini MS-based POC assays enable rapid, reliable quantification of clozapine and norclozapine, with performance comparable to conventional laboratory methods. This platform supports real-time TDM, facilitating timely dose adjustments, adherence monitoring, and ultimately improving patient outcomes.