Determination of iphosphamide and seven metabolites in blood plasma,as stable trifluoroacetyl derivatives,by electron capture chemical ionization GC-MS

A method is described for the determination of the antitumor agent iphosphamide and seven of its metabolites in the plasma of cancer patients by multiple ion monitoring (MIM) GC-MS, mainly using the electron capture chemical ionization mode, of stable methyl and/or trifluoroacetyl derivatives. The metabolites determined were 2- and 3-dechloroethyliphosphamide, 4-ketoiphosphamide, carboxyiphosphamide, iphosphamide mustard, and two previously undetected metabolites, chloroethylamine and 1,3-oxazolidine-2-one. The isolation of the acidic and neutral metabolites was performed by solid phase extraction on to C₁₈ adsorbent at pH 4. The weakly acidic iphosphamide mustard, isolated under these conditions with a yield of ca 50%, was measured as a stable methyltrifluoroacetyl derivative, in contrast to the corresponding phosphoramide mustard of the isomer cyclophosphamide which decomposes during derivatization. Chloroethylamine and 1,3-oxazolidine-2-one were isolated with high yield by liquid extraction with ethyl acetate at pH 10. Selective measurement of several metabolite derivatives with similar retention times was performed by multiple ion monitoring MS of specific ion masses, using a methyl phenyl siloxane capillary column previously employed in the study of cyclophosphamide metabolites. Quantitation of metabolites in patient plasma samples could be performed in the concentration range 3 ng to 20 μg per ml of original plasma.     

Atomistic phenomena in dense fluid shock waves

The shock structure problem is one of the classical problems of fluid mechanics and at least for non-reacting dilute gases it has been considered essentially solved. Here we present a few recent findings, to show that this is not the case. There are still new physical effects to be discovered provided that the numerical technique is general enough to not rule them out a priori. While the results have been obtained for dense fluids, some of the effects might also be observable for shocks in dilute gases.     

Stable model categories are categories of modules

A stable model category is a setting for homotopy theory where the suspension functor is invertible. The prototypical examples are the category of spectra in the sense of stable homotopy theory and the category of unbounded chain complexes of modules over a ring. In this paper we develop methods for deciding when two stable model categories represent ‘the same homotopy theory’. We show that stable model categories with a single compact generator are equivalent to modules over a ring spectrum. More generally stable model categories with a set of generators are characterized as modules over a ‘ring spectrum with several objects’, i.e., as spectrum valued diagram categories. We also prove a Morita theorem which shows how equivalences between module categories over ring spectra can be realized by smashing with a pair of bimodules. Finally, we characterize stable model categories which represent the derived category of a ring. This is a slight generalization of Rickard's work on derived equivalent rings. We also include a proof of the model category equivalence of modules over the Eilenberg-Mac Lane spectrum HR and (unbounded) chain complexes of R-modules for a ring R.     

Asymptotic behavior of tails and quantiles of quadratic forms of Gaussian vectors

We derive results on the asymptotic behavior of tails and quantiles of quadratic forms of Gaussian vectors. They appear in particular in delta–gamma models in financial risk management approximating portfolio returns. Quantile estimation corresponds to the estimation of the Value-at-Risk, which is a serious problem in high dimension.