Biolanalysis of ziprasidone and its S-methylated metabolite in serum using on-line extraction and liquid chromatography-masspectrometry
(English)Manuscript (preprint) (Other academic)
The novel antipsychotic agent Ziprasidone, (Zip) was introduced for clinical prescription in Sweden in the early spring of 2001. As of yet, no bioanalytical procedure suitable for a Therapeutic Drug Monitoring (TDM)-service of the drug has been presented. Therefore a bioanalytical methodology utilising online extraction on RP-C4-ADS columns combined with ion-trap masspectrometric detection for determination of Zip and its S-methylated metabolite (Smd-Zip) was developed. The stability of the analytes in serum was determined for establishing a correct sample handling procedure.
The calibration model for Zip and Smd-Zip had a linear response function in the concentration range 20 to 500 and 15 to 300 nM, respectively. The intra- and inter-day coefficient of variance was below 10% for all calibrator levels for both Zip and Smd-Zip. Validation of the sample handling procedure showed that samples are stable in room temperature or refrigerator for 3 days. Repeated freeze/thaw cycles, for five times did not affect the Zip or Smd-Zip concentration. In essence these findings state the importance of a correct sampling procedure for a functional ID M-procedure.
The TDM-procedure was applied on 10 patient serum samples obtained from a naturalistic clinical setting. The obtained concentrations, ranging from 66 to 432 nM for Zip and 42 to 220 nM for Smd-Zip were within the dynamic range of the present methodology. Thus, a future utility for this newly developed method in a TDM-setting seems evident.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84595OAI: oai:DiVA.org:liu-84595DiVA: diva2:560489