Abstract
This manuscript describes a sensitive, selective, and online in-tube solid-phase microextraction coupled with an ultrahigh performance liquid chromatography-tandem mass spectrometry (in-tube SPME-UHPLC-MS/MS) method to determine chlopromazine, clozapine, quetiapine, olanzapine, and their metabolites in plasma samples from schizophrenic patients. Organic poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith was synthesized on the internal surface of a fused silica capillary (covalent bonds) for in-tube SPME. Analyte extraction and analysis was conducted by connecting the monolithic capillary to an UHPLC-MS/MS system. The monolith was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR). The developed method presented adequate linearity for all the target antipsychotics: R2 was higher than 0.9975, lack-of-fit ranged from 0.115 to 0.955, precision had variation coefficients lower than 14.2%, and accuracy had relative standard error values ranging from −13.5% to 14.6%, with the exception of the lower limit of quantification (LLOQ). The LLOQ values in plasma samples were 10 ng mL−1 for all analytes. The developed method was successfully applied to determine antipsychotics and their metabolites in plasma samples from schizophrenic patients.
Highlights
Schizophrenia is a severe and chronic mental disorder characterized by profound disruptions in thinking, which affects language, perception, and the sense of self [1]
This disorder is characterized by positive, negative, and cognitive symptoms [1]
Atypical antipsychotics are the mainstay of treatment prescribed to schizophrenic patients
Summary
Schizophrenia is a severe and chronic mental disorder characterized by profound disruptions in thinking, which affects language, perception, and the sense of self [1]. This disorder is characterized by positive (psychotic behaviors), negative (disruptions to normal emotions and behaviors), and cognitive symptoms (changes in memory or other aspects of thinking) [1]. Atypical antipsychotics are the mainstay of treatment prescribed to schizophrenic patients. Studies have suggested that the pharmacokinetics of atypical antipsychotics involve large inter- and intra-individual differences among patients (age, gender, lifestyle, genetic and metabolic characteristics, and drug interactions). Therapeutic drug monitoring (TDM) can be extremely useful to establish an effective individual therapeutic dose that maintains plasma drug concentrations within a targeted therapeutic range, thereby avoiding an overdose [3,4]
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