Towards semi-quantitative mass spectrometry imaging of drugs in tissue

Turker, Sarah Didem (2020). Towards semi-quantitative mass spectrometry imaging of drugs in tissue. University of Birmingham. Ph.D.

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Abstract

Mass spectrometry has recently become a popular approach for the determination of the spatial distribution of drugs in vivo and in vitro, which has given rise to the field of mass spectrum imaging (MSI). A major challenge in this field is to make analysis quantitative, which relies on the construction of accurate calibration curves using standards that accurately simulate the ion suppression found in biological tissues. Another challenge is to rapidly screen tissues without resort to the labour intensive sample preparation associated with mass spectrum imaging. I hypothesise that these points may be addressed potentially by the use of drug spiked tissue homogenates in mass spectral analysis, which may both serve to act as accurate calibration standards that simulate ion suppression in tissues as well as being very straightforward to prepare. Hence in this thesis I address these points using the following methodology. In chapter 2, new calibration standards based on drug spiked liver tissue homogenates are used to produce calibration curves for a range of drugs. In chapter 3, liquid extraction sampling analysis (LESA) is used in combination with the spiked homogenate approach to produce calibration curves for fenclozic acid and propanolol. In both cases we show that semi-quantititative or quantitative calibration curves can be produced using tissue homogenates, which could potentially allow routine quantitative analysis to be made possible. In chapter 4 we use homogenates from excised animal subjects to compare against radiolabelling techniques used in industry (QWBA and LSC). We find that MALDI MS can detect the drugs, and if not the drug, the metabolites of the drugs, and it could be a useful tool for rapidly screening
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organs to ascertain which may merit further interrogation thus speeding up the process of drug discovery.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):