title: Enzymatic tumour tissue digestion coupled to SPE-UPLC-Tandem Mass Spectrometry as a tool to explore paclitaxel tumour penetration.
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.
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. Electronic address: Pieter.colin@ugent.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Colin
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Lieselotte
authors.initials: L
authors.lastname: De Smet
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: De Bock
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Goeteyn
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Boussery
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Bocxlaer
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D002138:Calibration; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D009132:Muscles / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000493:pharmacokinetics*; D051381:Rats; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: Enzymatic digestion; Paclitaxel; Solid phase extraction; Tumour tissue; UPLC–MS/MS