Structural identification of new glycolipids based on cyclodextrin using high-resolution positive and negative electrospray ionization mass spectrometry.

In the continuing challenge to increase the performance of cyclodextrins (CDs) for various applications, new phospholipidyl-cyclodextrin derivatives showing improved self-organization properties in water have been synthesized, as new carriers for drug vectorization, starting from natural beta-cyclodextrin. Due to the important chemical modifications of the original cyclic oligosaccharide molecules, simple nuclear magnetic resonance (NMR) experiments do not easily lead to both an unambiguous assignment of the structures and to a rapid evaluation of the purity of the final products. However, positive and negative ion electrospray ionization (ESI-MS) in combination with accurate mass measurements and tandem mass spectrometry (MS/MS) led to the positive structural identification of the first series of these new amphiphilic compounds.

Identification of an N-(hydroxysulfonyl)oxy metabolite using in vitro microorganism screening, high-resolution and tandem electrospray ionization mass spectrometry.

Preliminary metabolic profiling of a drug under pre-clinical development revealed the presence of a minor unknown metabolite with a positive ion electrospray ionization (ESI) mass spectrum identical to that of the unchanged compound. Since the low concentration of the compound did not allow any additional experiments, preparative bioconversion using fungi was used to obtain a substantial amount of the molecule. Negative ion ESI-MS and tandem mass spectrometry (MS/MS) in combination with accurate mass measurements obtained on a quadrupole/time-of-flight instrument (Q-TOF) led to the positive identification of a hydroxylamide sulfoconjugated metabolite.

Synthesis of putative metabolites and investigation of the metabolic fate of gliclazide, [1-(3-azabicyclo(3,3,0)oct-3-yl)-3-(4-methylphenylsulfonyl) urea], in diabetic patients.

Synthesis of postulated hydroxylated metabolites of gliclazide is described together with their detailed structural analysis using 1H-NMR, two-dimensional 1H-NMR, and MS to characterize the products. Metabolism of gliclazide has been investigated in the urine of nine patients of different ethnic origins receiving gliclazide therapy for the treatment of diabetes. Urine extracts were analyzed by GC/MS to quantify and identify the metabolites excreted in urine and the metabolites compared with the synthesized products.

Applications of liquid chromatography/dynamic liquid secondary ion mass spectrometry in structural elucidation studies.

The application of post-column splitting in liquid chromatography (LC) coupled to dynamic liquid secondary ion (or continuous-flow fast atom bombardment) mass spectrometry allows more flexibility with respect to the use of conventional LC methods. Gradient elution and the presence of involatile mobile phase modifiers do not therefore constitute insurmountable obstacles, especially in experiments where sensitivity is of secondary importance, such as in structural identification studies. The possibility of using conventional LC conditions presents a valuable gain in time by avoiding lengthy LC redevelopment procedures.

Chemical and glutathione conjugation-related degradation of fotemustine: formation and characterization of a glutathione conjugate of diethyl (1-isocyanatoethyl)phosphonate, a reactive metabolite of fotemustine.

Fotemustine is a chemotherapeutic drug for the treatment of melanoma. In this study, we investigated the metabolic and chemical stability of fotemustine with 31P-NMR and FAB-MS. In the absence of GSH, 95% of fotemustine decomposed rapidly into a reactive diethyl ethylphosphonate (DEP) isocyanate, both in rat liver S9 fraction and in HEPES buffer (pH = 7.