TDM of the atipical antipsychotics risperidone and paliperidone in plasma and DBS by LC-UV/MS: comparison of original analytical methods

The Therapeutic Drug Monitoring (TDM) is a powerful tool to optimise psychiatric therapies and reduce side and toxic effects, avoiding unnecessary and expensive hospitalisations and drug administrations. Risperidone is one of the most frequently prescribed atypical antipsychotic drugs, also approved for the treatment of manic-depressive disorders. Its main active metabolite, 9-hydroxyrisperidone, significantly contributes to its therapeutic effect; the sum of the two compound levels in blood (“active moiety”) is considered the clinically relevant concentration. This metabolite has been approved as an antipsychotic agent on its own, marketed under the name Paliperidone. In order to carry out a reliable TDM of patients treated with Risperidone and/or Paliperidone, it is necessary to develop innovative analytical strategies able to provide a reliable determination of the “active moiety” in blood and/or plasma. Two original methods based on LC-UV and MS have been developed for the simultaneous analysis of Risperidone and Paliperidone in plasma samples and in Dried Blood Spots (DBSs). DBSs represent an innovative and alternative biological matrix, which offers unique advantages in terms of compound stability, sampling and pre-treatment feasibility and analysis cost, while providing reliable and significant information. For sample purification, pre-treatment strategies by Solid Phase Extraction (SPE) and Microextraction by Packed Sorbent (MEPS) have been developed and validated. The results obtained comparing the two analytical methodologies are in good agreement, thus proving that both of them seem to be suitable for the TDM of psychiatric patients undergoing therapy with Risperidone and Paliperidone.