Clozapine Monitoring in Serum and Saliva

For several years, saliva has been investigated as an alternative matrix for therapeutic drug monitoring (TDM). Various studies have been carried out with different drugs. In contrast to previous studies, which took place in an inpatient setting, this study aimed to examine patients taking clozapine in an outpatient setting. The aim of the present study was therefore to identify and name possible influences on the success of this new kind of monitoring in outpatients.

In the period from May 2021 to May 2022, a total of 19 outpatients were included in the study. In addition to repeated blood samples, parallel saliva samples were collected as part of the TDM, up to ten parallel samples. Serum and saliva clozapine and N-desmethylclozapine concentrations were determined by HPLC-MS/MS.

Positive correlations between the serum and saliva concentrations over time of clozapine (r= 0.663) and its main metabolite N-desmethylclozapine (r= 0.222) were found. Clozapine and N-desmethylclozapine concentration time courses in saliva showed a strong correlation (r > 0.950) in 50% of participants, while in serum, the correlation was significant in 60% of participants. Clozapine and N-desmethylclozapine showed approximately 20% and 25% variation in serum, and 25% and 15% in saliva. In comparison, studies in inpatient settings reported higher coefficients of variation – 44% for clozapine and 29% for N-desmethylclozapine in saliva.

This study potentially contributes to the establishment of saliva as an alternative matrix for TDM. The notably low variation in saliva is promising, but further research is needed before this method can be widely used.

Publication History

Article published online:
12 March 2024