Smartdose

Simultaneous determination of multiple antibiotics by LC-MS/MS in plasma, tissue, and breath condensate for personalized antibiotic treatment

Adequate antibiotic treatment is the prerequisite for successful treatment of systemic infections. Increased scientific evidence shows that a fixed dosage regimen can lead to insufficient and ineffective antibiotic therapy. This is caused not only by the development of antibiotic resistance, but also by a changed pharmacokinetics (PK) in critically ill patients. To personalize the therapy a quantification of the plasma concentration of antibiotics by Therapeutic Drug Monitoring (TDM) can be applied.

The goal of the project Smartdose is to develop an LC-MS/MS-based method allowing simultaneous quantification of different antibiotics in serum or plasma. In addition, the newly developed method will be applied also to tissue samples and respiratory gas condensates in order to investigate whether the antibiotic concentration in plasma is associated with a sufficient amount at the site of action.

A TDM of piperacillin/tazobactam concentrations is the first application of the LC-MS/MS method, performed in a collaboration with the clinical trials Target and Target-FN. In addition, the establishment and validation of alternative methods (e.g. Raman spectroscopy) is planned in selected materials.

Figure: Example chromatogram for anti-infectives

The peaks are shown in an overall overview of positive and negative ionization, including retention times in a sample chromatogram for 1 mg/l of anti-infective agent in EDTA plasma. Left: Chromatogram of all analytes with positive ionization, right: Chromatogram of all analytes with negative ionization. (Master thesis Christina Wichmann 2016: Simultaneous quantification of clinically relevant anti-infectives in blood plasma using LC-MS / MS)