Study on the Decomposition of 2‐Chloroethylnitro‐ sosulfamides (CENS) in Serum Using HPLC On‐line Solid Phase Extraction

Abstract

In this paper we have investigated the kinetic decomposition of 2-chloroethylnitrososulfamides (CENS) in fetal calf serum. The study was monitored by on-line solid phase extraction linked to RP-LC-MS. We demonstrated that CENS are less stable in fetal calf serum than in aqueous buffer at pH 7.4 and 37 degrees C. Moreover, we have shown that partition coefficient of CENS can be correlated to the kinetics decomposition, and we observe that the stability is better for lipophilic CENS. The different metabolites after decomposition have been tentatively identified by RP-HPLC-MS. This study indicates the formation of several metabolites resulting from a mechanism of decomposition more complex than in aqueous phosphate buffer, nevertheless, leading to the same main products.

Inclusion complex of N-nitroso, N-(2-chloroethyl), N′, N′-dibenzylsulfamid with β-Cyclodextrin: Fluorescence and molecular modeling

“…To progress to clinical evaluation, additional data on the stability and mechanism of decomposition of CENS are needed. In order to gain a better understanding of the stability of this family of compounds, the first experimental investigation was carried out on the fragmentation of CENS in aqueous media and in serum using HPLC on-line solid phase extraction, LC-MS and conventional UV spectrophotometry [20,21].…”

Solvent effects of N‐nitroso, N‐(2‐chloroethyl), N′,N′‐dibenzylsulfamid and its copper(II) and cobalt(II) complexes: fluorescence studies

“…To gain insight into the stability of this family of compounds, the first experimental investigation was carried out on the fragmentation of CENS in aqueous media, by LC–MS and conventional UV spectrophotometry. In our group we have studied the kinetics of decomposition of CENSs in aqueous buffered solutions in the pH range 0–14 .…”

Inclusion Complexes of 2-Chloroethylnitrososulfamides (CENS) in Natural and Modified β – Cyclodextrins

“…The route for the preparation of CENS has been described in previous articles, and the first pharmacological evaluations have shown promising therapeutic applications [3][4][5][6]. However, aqueous decomposition studies of those *Address correspondence to these authors at the Laboratoire de chimie appliquée, Université de Guelma, BP 401, Guelma 24000, Algeria; E-mail: abdaoui_med@yahoo.fr IBMM, UMR 5247, Université Montpellier 2, CNRS, ENSCM, 8, rue de l'Ecole Normale, 34296 Montpellier cedex, France; E-mail: veronique.montero@univ-montp2.fr compounds demonstrated their relatively low stability [7,8]. Inclusion of CENS in cyclodextrins seems to be a promising way to improve their properties.…”