TITLE

Development of a high-throughput method for the determination of itraconazole and its hydroxy metabolite in human plasma, employing automated liquid–liquid extraction based on 96-well format plates and LC/MS/MS

AUTHOR(S)
Kousoulos, Constantinos; Tsatsou, Georgia; Apostolou, Constantinos; Dotsikas, Yannis; Loukas, Yannis L.
PUB. DATE
December 2005
SOURCE
Analytical & Bioanalytical Chemistry;Dec2005, Vol. 384 Issue 1, p199
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
A semi-automated liquid chromatography–tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous quantification of the antifungal drug itraconazole (ITZ) and its coactive metabolite hydroxyitraconazole (OH-ITZ) in human plasma. The plasma samples underwent liquid–liquid extraction (LLE) in 2.2 mL 96 deepwell plates. ITZ, OH-ITZ and the internal standard (IS) R51012 were extracted from plasma, using a mixture of acetonitrile (ACN) and methyl t-butyl ether (MTBE) as the organic solvent. This specific mixture, due to its composition, had a significant impact on the performance of the assay. All liquid transfer steps, including preparation of calibration standards and quality control samples as well as the addition of the IS, were performed automatically using robotic liquid handling workstations for parallel sample processing. After vortexing, centrifugation and freezing, the supernatant organic solvent was evaporated. The analytes and IS were dissolved in a small volume of a reconstitution solution, an aliquot of which was analyzed by combined reversed phase LC/MS/MS, with positive ion electrospray ionization and a TurboIonSpray interface, using multiple reactions monitoring (MRM). The method was shown to be sensitive and specific to both ITZ and OH-ITZ, it revealed excellent linearity for the range of concentrations 2–500 ng mL−1 for ITZ and 4–1000 ng mL−1 for OH-ITZ, it was very accurate and it gave very good inter- and intra-day precisions. The proposed high-throughput method was employed in a bioequivalence study after per os administration of two 100 mg tablets of ITZ, and it allowed this study to be completed in under four days.
ACCESSION #
19203918

 

Related Articles

  • Measurement of total homocysteine in plasma and blood spots using liquid chromatography–tandem mass spectrometry: comparison with the plasma Abbott IMx method. McCann, Steven J.; Gillingwater, Scott; Keevil, Brian G.; Cooper, Donald P.; Morris, Michel R. // Annals of Clinical Biochemistry;Mar2003, Vol. 40 Issue 2, p161 

    Background: Current sampling for total homocysteine (tHcy) is problematic, requiring plasma separation within 15 min. The aim of this study was to develop a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the measurement of tHcy in plasma and dried blood spots and to...

  • A SENSITIVE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRIC ASSAY FOR THE DETERMINATION OF ARTEMETHER AND ITS ACTIVE METABOLITE DIHYDROARTEMISININ IN HUMAN PLASMA. Tummuru, Bhanu Prakash; Pilli, Nageswara Rao; Bhukya, Babu Rao; Gowri Shankar, D. // International Journal of Pharmacy;2014, Vol. 4 Issue 1, p77 

    This paper describes a simple, rapid and sensitive liquid chromatography / tandem mass spectrometry (LC-MS/MS) assay method for the simultaneous quantification of artemether and its active metabolite, dihydroartemisinin in human plasma samples. Nevirapine was used as an internal standard....

  • UHPLC Coupled with Fourier Transform Orbitrap for Residue Analysis. Vanhaecke, Lynn; Verheyden, Karolien; Bussche, Julie Vanden; Schoutsen, Frans; De Brabander, Hubert // LC-GC Europe;Jul/Aug2009, Vol. 22 Issue 7, p364 

    The trend in residue analysis has changed from target-oriented procedures - mainly based on liquid chromatography combined with triple-quadrupole mass spectrometric (MS) detection � towards accurate mass full-scan MS techniques [e.g., time-of-flight (TOF) and Fourier transform mass...

  • Determination of Sunitinib and Its Active Metabolite N-Desethylsunitinib in Sweat of a Patient. Lankheet, Nienke A. G.; Blank, Christian U.; Mallo, Henk; Adriaansz, Sandra; Rosing, Hilde; Schellens, Jan H. M.; Huitema, Alwin D. R.; Beijnen, Jos H. // Journal of Analytical Toxicology;Oct2011, Vol. 35 Issue 8, p558 

    The article focuses on a study which determines sunitinib and its active metabolite N-desethylsunitib in human sweat. It depicts that skin reactions are side effects of sunitinib treatment with an adverse effect on quality of life often necessitating dose reductions. A sensitive and accurate...

  • Metabolism and pharmacokinetics of nibentan in human blood plasma. Appolonova, S.; Valiev, V.; Dikunets, M.; Kukharenko, A.; Rodchenkov, G.; Zeltyn', E.; Bezprozvannyi, A.; Gorshkov, V.; Radzevich, A. // Pharmaceutical Chemistry Journal;Jul2010, Vol. 44 Issue 7, p341 

    n HPLC method with electrospray ionization and ion-trap mass spectral detection (LC-ESI/MSD Ion Trap SL) for determining nibentan metabolites in human blood plasma is described. The proposed method provides simultaneous determination of nibentan and its metabolites in blood plasma. Three...

  • Optimization of Solid-Phase Extraction for the Liquid Chromatography—Mass Spectrometry Analysis of Harpagoside, 8-para-Coumaroyl Harpagide, and Harpagide in Equine Plasma and Urine. Cyril Colas; Patrice Garcia; Marie-Agnès Popot; Yves Bonnaire; Stéphane Bouchonnet // Journal of Chromatographic Science;Feb2008, Vol. 46 Issue 2, p174 

    Solid-phase extraction cartridges among those usually used for screening in horse doping analyses are tested to optimize the extraction of harpagoside (HS), harpagide (HG), and 8-para-coumaroyl harpagide (8PCHG) from plasma and urine. Extracts are analyzed by liquid chromatography coupled with...

  • Prednisolone measurement in human serum using liquid chromatography tandem mass spectrometry. Owen, LJ; Gillingwater, S; Keevil, BG // Annals of Clinical Biochemistry;Feb2005, Vol. 42 Issue 2, p105 

    Prednisolone is a commonly prescribed corticosteroid used in the treatment of many diseases. Despite high doses of prednisolone, some patients appear to have subtherapeutic concentrations of the drug. It would be useful to measure prednisolone in this group to determine if they have poor...

  • Physicochemical Properties and Stability of Anthralin in Model Systems and Human Skin. Sa E Melo, Théresa; Dubertret, Louis; Prognon, Patrice; Gond, Alain; Mahuzier, Georges; Santus, René // Journal of Investigative Dermatology;Jan1983, Vol. 80 Issue 1, p1 

    The physico-chemical properties and the stability of anthralin, a potent antipsoriatic agent, has been investigated in model systems by optical absorption and fluorescence spectroscopy and by gas chromatography coupled to mass spectrometry. Systematic studies were carried out on anthralin and...

  • UPLC-MS/MS determination of doxazosine in human plasma. Al-Dirbashi, Osama Y.; Aboul-Enein, Hassan Y.; Jacob, Minnie; Al-Qahtani, Khalid; Rashed, Mohamed S. // Analytical & Bioanalytical Chemistry;Sep2006, Vol. 385 Issue 8, p1439 

    A sensitive, selective and rapid method for the analysis of doxazosine (DOX) in human plasma based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) is described. DOX and tamsulosin, used as an internal standard (IS), were extracted by liquid-liquid extraction, and...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics