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Ahmed Issam Al-Kawaz

Validation and Determination of Candesartan with Different Juices in Rat Plasma
by using High Performance Liquid Chromatography/Mass Spectrometry
(HPLC/MS/MS).
By
Ahmed Issam Al-Kawaz
Supervisor:
Prof. Tawfiq Arafat
Co-Supervisor:
Dr. Wael Abu Dayyih
A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of
Master of Science in Pharmaceutical Sciences at
University of Petra
Faculty of Pharmacy and Medical Sciences
Amman-Jordan
January 2014
II
Validation and Determination of Candesartan with Different Juices in Rat Plasma
by using High Performance Liquid Chromatography/Mass Spectrometry
(HPLC/MS/MS).
By
Ahmed Issam Al-Kawaz
A Thesis Submitted in Partial Fulfillment of the Requirements for the
Degree of Master of Science in Pharmaceutical Science at
University of Petra
Faculty of Pharmacy and Medical Sciences
Amman-Jordan
January 2014
 
III
ABSTRACT
Validation and Determination of Candesartan with Different Juices in Rat Plasma
by using High Performance Liquid Chromatography/Mass Spectrometry
(HPLC/MS/MS).
By
Ahmed Issam Al-Kawaz
University of Petra, 2014
Supervisor Co-supervisor
Prof. Tawfiq Arafat Dr. Wael Abu Dayyih
A new validated simple, rapid and sensitive method for determination of candesartan in
the presence of each juice has been applied by using High Performance Liquid
Chromatography–Mass Spectrometry (HPLC/MS). The mobile phase was composed of
(methanol, of 0.2% FA in water) was used as a mobile phase, ACE 5 C18 Column (50 X
2.1 mm), 5μ, and a flow rate of 1.0 ml/min were used, the autosampler injection volume
was 5 microliters, and Irbesartan was used as internal standard, The precision of
predicted measurements for candesartan was high (mean CV% <10%). The accuracy for
candesartan over all the three days of validation and all the four tested target
concentration was within the accepted criteria. The standard curves for candesartan
matched the requirements, linear relation (R2) ranged between (0.996 to 1).
According to the result obtained, the Cmax for candesartan alone was (964.692 ng/ml),
there was no significant effect (P>0.05) of orange juice on candesartan Cmax
(1253.163ng/ml). and for Licorice, the Cmax was (818.2868 ng/ml) which is also
considered as a non- significant effect (P>0.05). on the other hand pomegranate shows to
decrease the Cmax of candesartan (475.9673 ng/ml) which is a significant effect
(P<0.05). candesartan plasma level was lowered to the half when combined with
pomegranate, and almost at the same level when combined with both of orange and
liquorice.
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ACKNOWLEDGEMENTS
In The Name of Allah, the Most Gracious, the Most Merciful
Foremost, I would like to express my special appreciation and thanks to my advisor Prof.
Tawfiq Arafat and my co-advisor Dr. Wael Abu Dayyih, you have been a tremendous
mentor for me. I would like to thank you for your patience, motivation, enthusiasm, and
immense knowledge. your guidance helped me in my research, allowing me to grow as a
research scientist. Your advice on both research as well as on my career have been
priceless. your influence on my life will continue through my entire life, as one of my
role models.
I would also like to thank my committee members, Prof. Zuhair Muhi-Eldeen, Dr. Eyad
Al-Mallah and Dr. Naseer Hashim Ahmed for serving as my committee members even at
hardship. I also want to thank you for letting my defense be an enjoyable moment, and
for your brilliant comments and suggestions, thanks to you.
To my family, Words cannot express how grateful I am to my mother Dr.Intisar, my
father Dr.Issam my brothers Anas and Zaid who spent sleepless nights with me and was
always my support in the moments when there was no one to answer my queries, Your
prayer for me was what sustained me thus far.
My sincere thanks to Prof. Tawfiq Alhussainy for his support and continuous advices
My sincere thanks also goes to Dr Nidal Qinna, for his support, advices and his help by
allowing using his laboratory, and to Mohammad Albayed, for his great technical
assistance in animal handling.
Special thanks to Hamza Al-Hurob from JCPR who have been very helpful and
supportive many thanks for the staff of JCPR who also helped me in this work.
For my dear friends, Marwa nasir, Mustafa nawzad, Noor Taqi, Rawnaq Jalal, Hagop,
Raghda Tobchi and Yaser Ahmed, I would like to specially thanking you for the help you
gave me, and your continuous spiritual support until the finish of this research.
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I would especially like to thank my dear friends, Teeba Emad, Rafal Ammar, Ahmed
Basim, Rafif Raad at University of Petra. All of you have been there to support me in
writing, and incented me to strive towards my goal.
Special thanks to my M.S.c friends (Abdullah Nabil, Nada Ali, Ibrahem Adil, Nibras
Jamal, Noor Maan, Ragheed Adil, Mujtaba, Zena Hilal and Zainab Al Obaidy).
Also I want to thank all my friends who have been very supportive. (Taha alKhanchi,
Maashar, Usama Mezil, Bashar Younis, Ban Thiab, Shahad Faisal, Ahmed Al-Azzawi,
Vegen, Mohannad Kattan, Hesham, Khalid Al-Haidari, Riham Nasir, Mais Jamal)
In the end, my thanks go to for my beloved brothers, my extended family, especially my
aunt Anaam. And I would love to dedicate this work, to my Father Dr.Issam and my
mother Dr,Intisar whom I know their prayers and love still protecting and guiding me.