Development, optimization and validation of analytical methods for the determination of antiepileptic drugs in biological samples - Application in clinical and forensic toxicology

Doctoral Dissertation uoadl:1305669 333 Read counter

Unit:
Τομέας Κλινικοεργαστηριακός
Library of the School of Health Sciences
Deposit date:
2016-06-14
Year:
2016
Author:
Νικολάου Παναγιώτα
Dissertation committee:
Σ. Αθανασέλης, Καθηγητής, Χ. Σπηλιοπούλου, Καθηγήτρια, Ι. Παπουτσής, Επικ. Καθηγητής
Original Title:
Ανάπτυξη, βελτιστοποίηση και επικύρωση μεθόδων προσδιορισμού αντιεπιληπτικών φαρμάκων σε βιολογικά υλικά - Εφαρμογές στην κλινική και δικαστική τοξικολογία
Languages:
Greek
Translated title:
Development, optimization and validation of analytical methods for the determination of antiepileptic drugs in biological samples - Application in clinical and forensic toxicology
Summary:
The aim of this thesis was the development, optimization and validation of gas
chromatography-mass spectrometric methods for the simultaneous determination of
antiepileptic drugs, in plasma and whole blood. During the method development,
the necessity appeared for separation of the antiepileptics according to their
chemical behavior. So, two methods were actually developed and validated, one
for the determination of the nine alkaline antiepileptics (ethosuximide,
carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine,
phenobarbital, phenytoin and topiramate) and two metabolites
(10,11-epoxide-carbamazepine and 10-hydroxy-carbazepine), and one for the
antiepileptics with acidic (valproic acid and tiagabine) and zwitterionic
(gabapentin, pregabalin and vigabatrin) behavior. The sample pretreatment
included protein precipitation with acetonitrile, solid phase extraction and
derivatization using MTBSTFA with 1% TBDMSCl at 70oC for 30min.
Levetiracetam-d6 was used as internal standard for the determination of
alkaline antiepileptics, whereas gabapentin-d10 was used for the acidic and
zwitterionic antiepileptics. The validation of the methods included the
evaluation of: selectivity, specificity and linearity, limits of detection and
quantification, intra- and inter-day accuracy and precision, absolute recovery
of the methods and the stability of analytes in spiked blood samples. The
developed methods were applied for therapeutic antiepileptic drug monitoring
and for the toxicological investigation of clinical and forensic cases.
Keywords:
epilepsy, antiepileptic drugs, plasma, blood, forensic and clinical toxicology
Index:
No
Number of index pages:
0
Contains images:
No
Number of references:
355
Number of pages:
xxiv, 283
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