Minimally invasive monitoring of clozapine: Correlation between dried blood spots and serum concentrations – a pilot study

Clozapine (CLO) is an atypical antipsychotic drug often used for treatment of pharmacoresistant schizophrenia. Therapeutic drug monitoring (TDM) is highly recommended in CLO therapy as optimal therapeutic range is narrow, high interindividual variability in plasma concentration exists and there is a significant risk of adverse drug reactions. TDM is traditionally based on venous blood sampling, which may be burdensome for patients and limits frequent monitoring. Dried blood spot (DBS) sampling represents a minimally invasive alternative, offering advantages in cost, stability, and ease of sample handling. This study aimed to characterize the relationship between CLO concentrations measured in DBS and serum. A total of 20 patient samples were collected, and CLO concentrations were determined in both matrices using an LC–MS method. Chromatographic separation was achieved on a Kinetex C18 column with gradient elution, and detection was performed using positive ionization on a maXis impact qTOF MS. Method optimization focused on sampling devices and extraction conditions. The method for determination of CLO in the DBS was validated accordingly to EMA guidelines. A strong correlation was observed between DBS and serum concentrations (r = 0.90, 95% CI 0.76–0.96). The effect of haematocrit was also evaluated. Our findings indicate that DBS sampling is a feasible alternative for CLO monitoring in clinical practice. However, due to systematic differences between matrices, and influence of haematocrit on agreement of concentrations DBS and serum, appropriate conversion for accurate interpretation is required, which should be validated in larger patient cohorts.