Butyl Methacrylate-Co-Ethylene Glycol Dimethacrylate Monolith for Online in-Tube SPME-UHPLC-MS/MS to Determine Chlopromazine, Clozapine, Quetiapine, Olanzapine, and Their Metabolites in Plasma Samples

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.

New insights into quetiapine metabolism using molecular networking

“…Indeed, this molecule undergoes an extensive and well-described metabolism. The existence of an abundant literature allows us to compare it with our data in order to assess their relevance [3][4][5][6][7] . In addition, it is an inexpensive and widely prescribed molecule.…”

“…Widely prescribed in these indications, this dibenzodiazepine derivative shows affinity for various neurotransmitter receptors including serotonin, dopamine, histamine and adrenergic receptors and has binding characteristics at the dopamine-2 receptor similar to those of clozapine 2 . Quetiapine undergoes an extensive liver biotransformation, involving cytochromes P450 (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) [3][4][5][6] . Among them, CYP3A4 and CYP2D6 are the predominant metabolic systems : CYP3A4 is known to give rise to N-desalkylquetiapine, N-desalkylquetiapine sulfoxide and quetiapine sulfoxide and CYP2D6 is known to give rise to 7-hydroxyquetiapine, 7-hydroxy-N-desalkylquetiapine 3,6,7 .…”

Bioanalytical HPLC Applications of In-Tube Solid Phase Microextraction: A Two-Decade Overview

“…Plasma and serum samples typically require deproteinization to prevent clogging of the capillary column. In the majority of the in-tube SPME applications, acetonitrile has been employed to facilitate protein precipitation in plasma samples [33][34][35]80,83,86,103,125,[134][135][136][137][138]. Alternatively pure methanol [121,140,141], 1% acetic acid in acetonitrile [79], or mixtures of acetonitrile/methanol 90/10 v/v have been also utilized for this purpose [139].…”

Poly (Octadecyl Methacrylate-Co-Trimethylolpropane Trimethacrylate) Monolithic Column for Hydrophobic in-Tube Solid-Phase Microextraction of Chlorophenoxy Acid Herbicides

“…Diverse SPE sorbents, such as highly cross-linked polystyrene-divinylbenzene sorbent [17], molecularly imprinted polymers [20,21], and cationic gemini surfactant-resorcinol-aldehyde resin [22], have been utilized for the extraction of CAHs. Monolithic columns, which could be synthesized in situ in the capillaries or tubes, have attracted increasing interests as an SPME sorbent because of their inherent advantages of facile preparation, diverse surface chemistry, increased enrichment capacity, and high porosity [27]. Recently, a multiple monolithic fiber which was reinforced by graphene has been proposed for extraction of CAHs [28].…”