UNIVERSITY OF CALGARY Effect of the human serum albumin concentration

UNIVERSITY OF CALGARY
Effect of the human serum albumin concentration
on the metabolism of cisplatin in vitro
by
Thomas Terry Morris
A THESIS
SUBMITTED TO THE FACULTY OF GRADUATE STUDIES
IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE
DEGREE OF MASTER OF SCIENCE
DEPARTMENT OF CHEMISTRY
CALGARY, ALBERTA
APRIL, 2014
© Thomas Terry Morris 2014

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Abstract
Size-exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic
emission spectrometer (ICP-AES) was employed to study the effect of the human serum albumin
(HSA) concentration on the metabolism of cisplatin (CP) in human blood plasma in vitro.
Plasma from 14 healthy adults and 11 pediatric cancer patients was spiked with CP and the Pt
distribution was determined at the 5 min and 2 hr time point. The results revealed that as the
HSA concentration decreased, the percent of Pt-bound to HSA decreased; whereas the percent of
Pt-hydrolysis products increased, while other Pt-species were largely unaffected. These changes
were corroborated by fortifying the cancer patient plasma with HSA to healthy concentrations
followed by the addition of CP. In summary, these findings imply that the infusion of cancer
patients with HSA to healthy plasma levels may decrease the fraction of free hydrolysis
products, which may alleviate the severe toxic side effects of CP.

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Acknowledgements
I would like to express my sincere gratitude to my supervisor Dr. Jürgen Gailer for giving
me the opportunity to work on these fascinating projects. His perpetual enthusiasm,
encouragement, and guidance have inspired me to broaden my knowledge and strengthen my
analytical skills.
I owe my deepest gratitude to Dr. Aru Narendran for his assistance and advice, as well as
for his help with the recruitment of cancer patients. I would also like to thank Karen Mazil for
her constant assistance with the ethics submission for this project, as well as with the recruitment
of the cancer patients.
I wish to express my warm and sincere thanks to Prof. Kevin Thurbide for being in my
supervisory committee and for all of the analytical knowledge he passed on. I am very grateful to
Dr. Roland Roesler for serving on my supervisory committee. It is a pleasure for me to thank Dr.
Ann-Lise Norman for accepting to be the internal examiner, and to Dr. Thomas Baumgartner for
being the neutral chair on my defense committee.
I am grateful to Mandy Chan at the Canadian Sport Centre, University of Calgary for
being so helpful in drawing blood from my volunteers for research. I would like to thank all of
the volunteers for being so generous to donate blood for my research.
Many thanks go to the Department of Chemistry administrative staff, especially to
Bonnie King and Janice Crawford for being so kind in clarifying all my questions. Alberta
Innovates Health Solution is greatly acknowledged for their financial support for my project, as
well as the University of Calgary for their financial support during my degree period.
It was a great pleasure to work with the past and current members of the Gailer group. I
would like to thank Melani and Elham for all of their help, advice, and support they provided

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during my degree. I greatly appreciated having them both around, and could not imagine better
group members to share this experience with.
Finally, I would like to convey my deepest gratitude to my parents and sister for their
love and support throughout my life, without whom I would not be where I am today. This
dissertation would not have been possible without all of you.

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Dedication
To my loving parents and sister…