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Enzymatic Tumour Tissue Digestion Coupled to SPE-UPLC-Tandem Mass Spectrometry as a Tool to Explore Paclitaxel Tumour Penetration

Enzymatic Tumour Tissue Digestion Coupled to SPE-UPLC-Tandem Mass Spectrometry as a Tool to Explore Paclitaxel Tumour Penetration

Pieter Colin, Lieselotte De Smet, Lies De Bock, Wim Goeteyn, Koen Boussery, Chris Vervaet, Jan Van Bocxlaer

Talanta. 2014 Nov;129:119-25.

PMID: 25127573

Abstract:

Paclitaxel is a good compound for regional (intraperitoneal) chemotherapy of peritoneal carcinomatosis. During IPEC, a cytotoxic solution is circulated in the peritoneal cavity, thereby promoting close contact between the cytotoxic agent and the exposed (residual) tumour tissue. To further explore the role of PTX in this type of treatment and study the impact of treatment modalities on tumour tissue penetration, in-vivo animal experiments were set-up. In literature, PTX tumour uptake is frequently studied using autoradiography and/or fluorescence microscopy techniques. Owing to their semi-quantitative nature on one hand and the difficulty of incorporating imaging data within a pharmacokinetic-pharmacodynamic modelling framework on the other hand, we set out to develop a validated assay for the quantification of PTX in tumour tissue samples. Furthermore, in order to maximise spatial resolution, care was taken to minimise the sample weight necessary for the analysis. Based on an enzymatic tumour tissue digestion protocol, an easy, less labour-intensive, when compared to mechanical tissue disruption techniques, method was developed. Through validation experiments we showed that our method reliably quantifies PTX in a working range of 30-8000 ng/g tumour tissue. Finally, using samples from the in-vivo experiments we demonstrated the suitability of the developed method.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42610	Mass scale and resolution set-up solution			Price

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