Date of Award

2018

Degree Type

Thesis

Degree Name

Master of Science in Chemistry

Department

Chemistry

First Advisor

Guo, Baochuan

Subject Headings

Analytical Chemistry, Biochemistry, Chemistry

Abstract

Bleomycin is the most commonly used compound in its group of antineoplastic drugs. It works on tumor cells by single and double stranded DNA cleavage after its activation, in which it blocks tumor cells’ DNA replication or transcription activities to inhibit tumor cells’ growth. Bleomycin sulfate (Blenoxane) is the most popular preparation used in clinical research, and contains Bleomycin fractions of A2 and B2, which causes difficulties in quantitative analysis. This work uses the metal chelating property of Bleomycin as an advantage to simplify and improve sensitivity of existing quantitative methods. Copper was spiked in excess to plasma samples, followed by liquid-liquid extraction. Samples were then subjected to analysis by high-performance liquid chromatography electrospray ionization tandem mass spectrometry using a quadrupole trap mass analyzer. Samples spiked with copper showed improved selectivity over samples without excess copper, thereby making use of standard mass spectrometers a possibility in the clinic. In comparison with current methods of quantification of Bleomycin in plasma, this method achieved higher percent recoveries of the chemotherapy drug, higher sensitivity of quantification, with lower matrix effects, as well as a more simple preparation method. Linear range in the lower nanogram per milliliter range with a correlation coefficient over 0.99 makes this method promising for improved quantification and monitoring of Bleomycin in plasma.

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