Development of modified antibiotics as internal standards for therapeutic drug monitoring

Abstract

Since antibiotics are used to treat various bacterial infectious diseases there is a fight against bacterial resistance. As the concentration of the antibiotic in the blood is of great interest there is the need of measuring this concentration over time.This is called therapeutic drug monitoring (TDM). Some issues in the use of immunoassays favor LC-MS techniques to be used. For quantification in LC-MS an internal standard is needed where nowadays isotope labeled standards are used. The drawbacks of these are that they are expensive, not easy to synthesize and therefore have a limited availability. To cope with these issues the goal of the QUANTIS project as a cooperation betweenTU Vienna and ARCHIMEDlife® is to synthesize new internal standards via small modifications of the actual antibiotic.The modifications have to be so small that the chemical similarity needed to be a valid internal standard is still given. So, the idea was to tailor those quantification standards (TQS) to fit for their purpose. Various reactions such as homologation, conjugation and oxidation were considered to modify the antibiotics.In this thesis new potential TQS for antibiotics out of the class of β-lactams and aminoglycosides could be synthesized and one of them could also be validated so far.