pharma-2018-scientifictracks

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Pharma 2018
Page 23
E u r o p e a n C o n g r e s s o n
Pharma
A u g u s t 1 3 - 1 4 , 2 0 1 8
P a r i s , F r a n c e
American Journal of Pharmacology and Pharmacotherapeutics
ISSN: 2393-8862
Vandetanib ( VNT) is an oral inhibitor of vascular endothelial growth factor
receptor. The current work reports the identification and characterization
of in vitro and reactive metabolites of VNT. In vitro metabolites of VNT
were generated by incubation with rat liver microsomes (RLMs). Extraction
of vandetanib and its in vitro metabolites from the incubation mixtures were
done by protein precipitation method. N-methyl piperidine ring of vandetanib,
a cyclic tertiary amine, undergoes metabolism to form iminium intermediates
that are reactive toward nucleophilic macromolecules. Incubation with RLMs
in the presence of 1.0 mM KCN to check reactive metabolites as it is often
responsible for observed idiosyncratic toxicities including phototoxicity and
prolongation of QT interval. Six in vitro phase I metabolites, and four cyano
conjugates of vandetanib were detected by LC-MS/MS. In vitro phase I
metabolic pathways were N-demethylation, N-oxide formation, α-carbonyl
formation and α-hydroxylation. All metabolic reactions occurred in N-methyl
piperidine of vandetanib which causes its instability and toxicity. Validated LC–
MS/MS was established for the determination of VNT in rat liver microsomes
(RLMs) . This method was applied in metabolic stability investigation of VNT.
Resolution of two analytes was performed using C18 column and isocratic
mobile phase composed of binary system of 10 mM ammonium formate
(pH 4.1) and acetonitrile in a ratio of 1:1. The flow rate was set at 0.25 mL/
min and total run time was 4 min with injection volume of 5 µL. Ions were
generated by ESI source and analyzed by multiple reaction monitoring mode
(basis for quantification) in the Agilent 6410 QqQ analyzer. The linearity of the
established method ranged from 5 to 500 ng/mL (r2 ≥ 0.9996) in RLMs. LOQ
and LOD was 7.52 ng/mL, and 6.49 in RLMs matrices. The intra-day and inter-
day precision and accuracy in RLMs matrix, ranged from 0.97 to 3.08% and
95.8 to 100.09% . In vitro half-life was 39.85 min and intrinsic clearance was
3.92±0.28 mL/min/kg.
Biography
Sawsan M Amer, starting higher school in 1972, obtained her
Bachelors’ in Pharmaceutical chemistry, 1977. She worked as
Pharmaceutical Researcher in National Research Centre from
1977-1980 and obtained her MSc in 1980 fromCairo University,
faculty of pharmacy, Egypt. She has joined as Assistant Lecturer
1980, became Lecturer in 1985 and Assistant Professor in
Analytical Chemistry Department, Faculty of Pharmacy Cairo
University in 1995. She has completed her PhD in 1985 from
Cairo University. She is Full Professor from 2003-present
and Head of Analytical Chemistry Department, Faculty of
pharmacy, Cairo University from 2010- 2015. She has worked
as a Lecturer in Faculty of Science in 1993 and as a Professor
in College of Pharmacy, King Saud University, Saudi Arabia.
She has published more than 65 papers in reputed journals
and has been serving as an Editorial Board Member of Bulletin,
Faculty of pharmacy, Cairo University and Reviewer in journal
of Talanta, Analytical Chemica Acta, Spectrochemica Acta,
Saudi Pharmaceutical Journal &many others. She is a Member
of the Syndicate of Pharmacists, the Professional Society of
Pharmacists, Egypt, the Society of Analytical Chemistry, Egypt ,
and in the Society of Saudi Chemists. She has supervised about
30 Master and PhD theses. Also she was involved in judging
committee for more than 25 theses.
Identification and characterization of in vitro and reactive
metabolites of vandetanib in RLMs with method quantification
using LC-MS/MS: application to metabolic stability
Sawsan M Amer1 , Adnan A Kadi 2, Hani W Darwish1, 2 and
Mohamed W Attwa1, 2
1Cairo University, Egypt
2King Saud University, Saudi Arabia
Sawsan M Amer et al., Am J Pharmacol Pharmacother 2018, Volume 5
DOI: 10.21767/2393-8862-C1-002