The use of dried blood spots as sample collection for the therapeutic drug monitoring of atypical antipsychotics

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Introduction: The collection of blood samples on filter papers, known as dried blood spots (DBS), is an established technique for the screening of newborn errors of metabolism. Recently, there is a large evidence for its use in the therapeutic drug monitoring (TDM) field for the quantitative analysis of small molecules. The collection of whole blood as DBSs has many advantages in comparison to conventional plasma sampling: smaller sample volumes, less invasive withdrawal, easier storage and shipment, less requirements for biohazard arrangements. In the last decade numerous analytical methods have been developed in our Laboratory of Pharmaco-Toxicological Analysis for the plasmatic monitoring of several Central Nervous System drugs in collaboration with national and foreign Psychiatric Clinics. Thus, the DBS technique as sample collection could be advisable for TDM purposes of atypical antipsychotics. Methods: Some analytical methods by means of high performance liquid chromatography coupled with both electrochemical and spectrophotometric detectors have been implemented for the analysis of clozapine, olanzapine, risperidone and aripiprazole in DBSs from psychiatric patients. Blood was spotted onto filter papers and allowed to dry. The quantitative assays employed simple solvent extraction of the analytes from the DBS samples, followed by solid-phase extraction (SPE) or micro-SPE procedures for the clean-up of the biological samples. Results: Preliminary results showed good extraction yield values of clozapine and risperidone from DBSs, being always higher than 85.0%. Results were satisfactory in terms of sensitivity and selectivity. Moreover, preliminary stability data showed that the samples in the DBS form can be stored for a long period of time before the analysis without the need of refrigeration or any particular arrangements. Clozapine and risperidone levels obtained from DBSs were in good agreement with those obtained from plasma analysis [1,2] after multiplying the DBS values by 1.8. Discussion: Assays are currently in progress to validate the methods in terms of linearity, precision and accuracy and to apply them to TDM of numerous patients treated with clozapine, olanzapine, risperidone and aripiprazole.