Ανάπτυξη και επικύρωση μεθόδου Υγροχρωματογραφίας Υδρόφιλης Αλληλεπίδρασης-Φασματομετρίας μαζών για τον ποσοτικό προσδιορισμό του Deferasirox σε ανθρώπινο πλάσμα.

Postgraduate Thesis uoadl:1315970 297 Read counter

Unit:
Κατεύθυνση Έλεγχος Φαρμακευτικών Ενώσεων (Φαρμακευτική Ανάλυση)
Library of the School of Science
Deposit date:
2012-07-05
Year:
2012
Author:
Πληγοροπούλου Ελένη
Supervisors info:
Αναπλ. Καθηγήτρια Παντερή Ειρήνη (επιβλέπουσα), Μ. Κουππάρης Καθηγ., Γ. Κουππάρης Καθηγ.
Original Title:
Ανάπτυξη και επικύρωση μεθόδου Υγροχρωματογραφίας Υδρόφιλης Αλληλεπίδρασης-Φασματομετρίας μαζών για τον ποσοτικό προσδιορισμό του Deferasirox σε ανθρώπινο πλάσμα.
Languages:
Greek
Summary:
The clinical course of patients with β-thalassemia major is characterised by
profound anaemia, who present to medical attention in the first year of life,
and who subsequently require regular blood transfusions and iron chelation
therapy for survival. Excess iron is deposited in the form of hemosiderin
primarily in the liver, spleen, several endocrine organs, and myocardium and
leads to progressive organ dysfunction and ultimately death. Iron overload can
also be caused in patients with sickle cell disease as a result of repeated
blood transfusions and in patients with chronic anemias or hereditary
hemochromatosis because of excessive dietary iron uptake.
Deferasirox,
4-[(3Z,5E)-3,5-bis(6-oxocyclohexa-2,4-dien-1-ylidene)-1,2,4-triazolidin-1-yl]
benzoic acid, is an orally absorbed tridentate bis hydroxyl pheny-triazol
chelator of Fe3+. A validated method based on liquid chromatography/ positive
ion electrospray- mass spectrometry (LC/ESI-MS) is described for the
quantification of deferasirox, in human plasma. The assay was based on 50 μL
plasma samples, following liquid-liquid extraction using ethyl acetate as an
extraction solvent. The analyte and the internal standard (mirtazapine) were
separated by hydrophilic interaction liquid chromatography using an Xbridge
HILIC analytical column (150.0 x 2.1mm i.d., particle size 3.5μm, 135A) with
isocratic elution. The mobile phase consisted of 10% 8.0 mM ammonium acetate
water solution pH=5.0, adjusted with formic acid, in a binary mixture of
acetonitrile/methanol (50:50, v/v) and pumped at a flow rate of 0.20 mL min-1.
Quantitation of deferasirox was performed with selected ion monitoring (SIM) in
positive ionization mode using electrospray ionization interface. The assay was
found to be linear in the concentration range of 0.20-120.0 μg mL-1 for
deferasirox. Intermediate precision were found less than 3.9% over the tested
concentration ranges. A run time of less than 6.0 min for each sample made it
possible to analyze a large number of human plasma samples per day. The method
is the first reported application of HILIC in the analysis of deferasirox and
can be used to support a wide range of clinical studies concerning deferasirox
monitoring.
Keywords:
Deferasirox, HILIC, MS, B-thalassemia, Plasma
Index:
Yes
Number of index pages:
6-7
Contains images:
Yes
Number of references:
86
Number of pages:
100

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