Details

Autor(en) / Beteiligte

• Wojnicz, Aneta
• Belmonte, Carmen
• Koller, Dora
• Ruiz-Nuño, Ana
• Román, Manuel
• Ochoa, Dolores
• Abad-Santos, Francisco

Titel

Effective phospholipids removing microelution-solid phase extraction LC-MS/MS method for simultaneous plasma quantification of aripiprazole and dehydro-aripiprazole: Application to human pharmacokinetic studies

Ist Teil von

• Journal of pharmaceutical and biomedical analysis, 2018-03, Vol.151, p.116-125

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• [Display omitted] •Mass spectrometry to monitor aripiprazole and its metabolite plasma levels.•Fast microelution solid phase extraction as sample preparation method.•Effective plasma phospholipids removal.•Method validated according to the recommendations of regulatory agencies.•Application to the pharmacokinetic study of healthy volunteers. A simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of aripiprazole and its active metabolite, dehydro-aripiprazole, in human plasma. Stable isotopically labeled aripiprazole, aripiprazole-D8, has been used as the internal standard (IS) for both analytes. Only 200 μl of human plasma was needed for analyte extraction, using effective phospholipids-eliminating three-step microelution-solid-phase extraction (SPE, Oasis PRiME HLB 96-well μElution Plate). An ACE C18-PFP column was applied for chromatographic separation at 25 °C, protected by a 0.2-μm on-line filter. A combination of ammonium formate (5 mM)-acetonitrile (pH 4.0; 65:35, v/v) was used as mobile phase and the chromatogram was run under gradient conditions at a flow rate of 0.6 ml/min. Run time lasted 5 min, followed by a re-equilibration time of 3 min, to give a total run time of 8 min. Five μl of the sample was injected into the chromatographic system. Aripiprazole, dehydro-aripiprazole and IS were detected using the mode multiple reaction monitoring in the positive ionization mode. The method was linear in the concentration range of 0.18–110 ng/ml and 0.35–100 ng/ml for aripiprazole and dehydro-aripiprazole, respectively. Our method has been validated according to the recommendations of regulatory agencies through tests of precision, accuracy, recovery, matrix effect, stability, sensitivity, selectivity and carry-over. Our microelution-SPE method removes more than 99% of main plasma phospholipids compared to protein precipitation and was successfully applied to several bioequivalence studies.