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.

This work describes the direct coupling of the in-tube solid-phase microextraction (in-tube SPME) technique to a tandem mass spectrometry system (MS/MS) to determine amino acids (AA) and neurotransmitters (NT) (alanine, serine, isoleucine, leucine, aspartic acid, glutamic acid, lysine, methionine, tyrosine, and tryptophan) in plasma samples from schizophrenic patients. An innovative organic-silica hybrid monolithic capillary with bifunctional groups (amino and cyano) was developed and evaluated as an extraction device for in-tube SPME. The morphological and structural aspects of the monolithic phase were evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), nitrogen sorption experiments, X-ray diffraction (XRD) analyses, and adsorption experiments. In-tube SPME-MS/MS conditions were established to remove matrix, enrich analytes (monolithic capillary) and improve the sensitivity of the MS/MS system. The proposed method was linear from 45 to 360 ng mL−1 for alanine, from 15 to 300 ng mL−1 for leucine and isoleucine, from 12 to 102 ng mL−1 for methionine, from 10 to 102 ng mL−1 for tyrosine, from 9 to 96 ng mL−1 for tryptophan, from 12 to 210 ng mL−1 for serine, from 12 to 90 ng mL−1 for glutamic acid, from 12 to 102 ng mL−1 for lysine, and from 6 to 36 ng mL−1 for aspartic acid. The precision of intra-assays and inter-assays presented CV values ranged from 1.6% to 14.0%. The accuracy of intra-assays and inter-assays presented RSE values from −11.0% to 13.8%, with the exception of the lower limit of quantification (LLOQ) values. The in-tube SPME-MS/MS method was successfully applied to determine the target AA and NT in plasma samples from schizophrenic patients.

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