Simultaneous determination of six antipsychotics, two of their metabolites and caffeine in human plasma by LC-MS/MS using a phospholipid-removal microelution-solid phase extraction method for sample preparation.
Talanta
; 198: 159-168, 2019 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-30876545
ABSTRACT
A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in human plasma for the simultaneous determination of aripiprazole (ARI) and its metabolite dehydro-aripiprazole (DARI); olanzapine (OLA), risperidone (RIS), paliperidone (PAL), quetiapine (QUE), clozapine (CLO) and caffeine (CAF). CAF is included to the method because it can have an influence on drug metabolism due to competitive inhibition. The above mentioned compounds and their isotope-labeled internal standards were extracted from 200⯵L human plasma samples by both, effective phospholipids-eliminating three-step microelution-solid-phase extraction (µ-SPE) and protein precipitation (PPT) for comparison. A combination of formic acid (0.2%)-acetonitrile (pH 3.0; 6535, v/v) was used as mobile phase and the chromatogram was run under gradient conditions at a flow rate of 0.6â¯mL/min. Run time lasted 6â¯min, followed by a re-equilibration time of 3â¯min. All analytes were monitored by mass spectrometric detection operating in multiple reaction monitoring mode and the method was validated covering the corresponding therapeutic ranges 0.18-120â¯ng/mL for ARI, 0.25-80â¯ng/mL for DARI, 1.00-100â¯ng/mL for OLA, 0.70-60â¯ng/mL for RIS, 0.20-30â¯ng/mL for PAL, 0.50-160â¯ng/mL for QUE, 0.50-1000â¯ng/mL for CLO, and finally 1200-3700â¯ng/mL for CAF. The method was validated based on the recommendations of regulatory agencies through tests of precision, accuracy, extraction recovery, identity confirmation, trueness, matrix effect, process efficiency, stability, selectivity, linearity and carry-over effect fulfilling the guideline requirements. Our µ-SPE method results in the elimination of more than 99% of early eluting and more than 92% of late-eluting phospholipids compared to PPT. Additionally, the method was successfully applied for quantifying ARI and OLA plasma concentrations from healthy volunteers.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfolípidos
/
Antipsicóticos
/
Cafeína
/
Extracción en Fase Sólida
/
Aripiprazol
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Revista:
Talanta
Año:
2019
Tipo del documento:
Article