HPLC method for determination of biologically active epoxy-transformers of treosulfan in human plasma: pharmacokinetic application.

  title={HPLC method for determination of biologically active epoxy-transformers of treosulfan in human plasma: pharmacokinetic application.},
  author={Franciszek K. Gł{\'o}wka and Michał Romański and Artur Tężyk and Czesław Żaba and Tomasz Wr{\'o}bel},
  journal={Journal of pharmaceutical and biomedical analysis},

Development and Validation of a High Pressure Liquid Chromatography-UV Method for the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its Application in Pharmacokinetic Studies.

A simple, sensitive high performance liquid chromatography method for the determination of the sum of treosulfan and its epoxy metabolites by UV detection after derivatization with sodium diethyldithiocarbamate in human plasma was developed and validated and met the analytical criteria.

Activation of Prodrug Treosulfan at pH 7.4 and 37°C Accompanied by Hydrolysis of Its Active Epoxides: Kinetic Studies with Clinical Relevance.

The kinetics of the nonenzymatic transformation of TREO in the presence of plasma electrolytes cannot contribute to the very low levels of S,S-EBDM and S, S-DEB observed in patient plasma.

Pharmacokinetics of treosulfan and its active monoepoxide in pediatric patients after intravenous infusion of high-dose treosulfan prior to HSCT.

  • F. GłówkaA. Kasprzyk C. Żaba
  • Medicine, Biology
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2015



Determination of epoxides by high-performance liquid chromatography following derivatization with N,N-diethyldithiocarbamate

The method is robust, and as low as 5 pmol of the analyte could be successfully detected and quantified with recoveries of ≥94%.

Clinical pharmacokinetics of intravenous treosulfan in patients with advanced solid tumors

A clinical phase I pharmacokinetics and dose-escalation trial with autologous blood stem-cell support has been started at 20 g/m2 treosulfan using a 2-h infusion protocol.

A simplified methodology for quantitation of butadiene metabolites. Application to the study of 1,3-butadiene metabolism by rat liver microsomes.

  • X. ChengJ. A. Ruth
  • Chemistry
    Drug metabolism and disposition: the biological fate of chemicals
  • 1993
It is demonstrated that the epoxy diol, although not extractable from aqueous solutions by ethyl acetate, can be recovered upon evaporation of aqueously media, followed by ethanol acetate extraction, and facilitated the examination of butadiene metabolism by rat liver microsomes.

The role of hydrolysis in the detoxification of 1,2:3,4-diepoxybutane by human, rat, and mouse liver and lung in vitro.

The observation that GSH conjugation of BDE is a potentially mutagenic pathway, explain the high susceptibility of mice to BD-induced carcinogenesis and the heterogeneity among humans in the formation as well as in the removal of Bde will be an important factor in human risk assessment.

Electrospray ionization detection of inherently nonresponsive epoxides by peptide binding.

This study demonstrates the possibility of assaying epoxides bound to peptides or proteins in biological samples and demonstrates an important concept that could be applied to other analytical problems in electrospray: the ability to react an analyte that is nonresponsive to electrosPRay analysis with an analyzete well suited for the technique, and accomplish quantitation based on the adduct formed between the two.

Oxidation of butadiene monoxide to meso- and (+/-)-diepoxybutane by cDNA-expressed human cytochrome P450s and by mouse, rat, and human liver microsomes: evidence for preferential hydration of meso-diepoxybutane in rat and human liver microsomes.

Results, which characterize new metabolic reactions for BM and DEB, may be of toxicological importance, as significant species differences reflecting both the stereoselective oxidation of BM by P450 enzymes and the subsequent preferential meso-DEB hydration by epoxide hydrolase have been demonstrated.