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Tytuł:
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A sensitive capillary LC-UV method for the simultaneous analysis of olanzapine, chlorpromazine and their FMO-mediated N-oxidation products in brain microdialysates.
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Autorzy:
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Hendrickx S; KU Leuven, Pharmaceutical Analysis, Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, 3000 Leuven, Belgium.
Uğur DY; Anadolu University, Faculty of Pharmacy, Department of Analytical Chemistry, 26470 Eskisehir, Turkey.
Yilmaz IT; Anadolu University, Faculty of Pharmacy, Department of Analytical Chemistry, 26470 Eskisehir, Turkey.
Şener E; Anadolu University, Faculty of Pharmacy, Department of Analytical Chemistry, 26470 Eskisehir, Turkey.
Van Schepdael A; KU Leuven, Pharmaceutical Analysis, Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, 3000 Leuven, Belgium.
Adams E; KU Leuven, Pharmaceutical Analysis, Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, 3000 Leuven, Belgium.
Broeckhoven K; Vrije Universiteit Brussel, Department of Chemical Engineering, Pleinlaan 2, 1050 Brussel, Belgium.
Cabooter D; KU Leuven, Pharmaceutical Analysis, Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, 3000 Leuven, Belgium. Electronic address: .
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Źródło:
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Talanta [Talanta] 2017 Jan 01; Vol. 162, pp. 268-277. Date of Electronic Publication: 2016 Sep 28.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Amsterdam : Elsevier
Original Publication: Oxford : Pergamon Press
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MeSH Terms:
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Benzodiazepines/*analysis
Brain/*metabolism
Chlorpromazine/*analysis
Chromatography, High Pressure Liquid/*methods
Dialysis Solutions/*chemistry
Animals ; Antipsychotic Agents/analysis ; Antipsychotic Agents/pharmacokinetics ; Benzodiazepines/pharmacokinetics ; Chlorpromazine/pharmacokinetics ; Male ; Microdialysis/methods ; Olanzapine ; Oxidation-Reduction ; Oxides/analysis ; Oxygenases/metabolism ; Rats, Wistar ; Reproducibility of Results
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Contributed Indexing:
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Keywords: Capillary LC; Chlorpromazine; FMO; MEPS; Microdialysis; Olanzapine
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Substance Nomenclature:
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0 (Antipsychotic Agents)
0 (Dialysis Solutions)
0 (Oxides)
12794-10-4 (Benzodiazepines)
EC 1.13.- (Oxygenases)
EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming))
N7U69T4SZR (Olanzapine)
U42B7VYA4P (Chlorpromazine)
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Entry Date(s):
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Date Created: 20161114 Date Completed: 20180917 Latest Revision: 20181202
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Update Code:
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20240104
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DOI:
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10.1016/j.talanta.2016.09.053
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PMID:
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27837829
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A specific and sensitive capillary liquid chromatography-ultraviolet detection (cap-LC-UV) method in combination with a micro-extraction by packed sorbent (MEPS) sample clean-up procedure has been developed and validated for the simultaneous analysis of chlorpromazine, olanzapine and their flavin-containing monooxygenase (FMO) mediated N-oxides in rat brain microdialysates. Chromatographic separation was obtained on an Acclaim Pepmap RP C18 column with an ID of 300µm. An injection volume of 20µL was used to inject the largely aqueous samples and was shown to have no influence on the obtained peak shape of the compounds of interest. Optimal conditions for MEPS extraction were obtained on a mixed-mode M1 (80% C8, 20% SCX) cartridge after diluting microdialysate samples with phosphate buffer pH 2.5 (1:3 v/v). The method was validated and lower limits of quantification (LLOQ) were determined at 0.5nM for all compounds. Linearity was demonstrated between the LLOQ and 1µM for all compounds (R 2 >0.995). MEPS recoveries were between 92% and 98%, with intra- and interday variabilities below 15%. The applicability of the developed method was successfully demonstrated by analysing rat brain microdialysates. The capillary LC-UV method in combination with MEPS sample treatment provides a simple, sensitive method to quantify all compounds of interest in 45min and can be applied for routine therapeutic monitoring and pharmacokinetic studies of olanzapine, chlorpromazine and their respective N-oxides.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
