Polymeric nanoparticles have become indispensable in modern society with a wide array of applications ranging from waterborne coatings to drug-carrier-delivery systems. While a large range of techniques exist to determine a multitude of properties of these particles, relating physicochemical properties of the particle to the chemical structure of the intrinsic polymers is still challenging. A novel, highly orthogonal separation system based on comprehensive two-dimensional liquid chromatography (LC × LC) has been developed. The system combines hydrodynamic chromatography (HDC) in the first-dimension to separate the particles based on their size, with ultrahigh-performance size-exclusion chromatography (SEC) in the second dimension to separate the constituting polymer molecules according to their hydrodynamic radius for each of 80 to 100 separated fractions. A chip-based mixer is incorporated to transform the sample by dissolving the separated nanoparticles from the first-dimension online in tetrahydrofuran. The polymer bands are then focused using stationary-phase-assisted modulation to enhance sensitivity, and the water from the first-dimension eluent is largely eliminated to allow interaction-free SEC. Using the developed system, the combined two-dimensional distribution of the particle-size and the molecular-size of a mixture of various polystyrene (PS) and polyacrylate (PACR) nanoparticles has been obtained within 60 min.

The degradation kinetics of various oxazaphosphorines : trofosfamide, cyclophosphamide, and 2-and 3-dechloroethylifosfamide was studied by means of a high-performance liquid chromatographic method. The results were compared with the kinetics of ifosfamide. It appeared that the presence and the site of the chloroethyl group influenced the chemical stability of the compounds.Cytostatic drugs are among the most unstable compounds in clinical use. Their cytotoxic action and the reactivity of these compounds are highly related to their lability.The oxazaphosphorines, cyclophosphamide (CP), ifosfamide (IF), and trofosfamide (TF) are alkylating cytostatic agents (Fig 1). The chemical stability of IF has been studied earlier.' The compound shows a threephase pH-degradation profile consisting of a hydroxyl-, proton-, and solvent-catalyzed part. During the degradation of IF in alkaline aqueous solution, a degradation product can be detected. In the present study the influence of the chloroethyl group(s) on the degradation kinetics of the oxazaphosphorines was studied by means of a high-performance liquid chromatographic (HPLC) system. For this purpose, two metabolites of IF also were included in the studies. The 2-and 3-dechloroethylifosfamide (2-and 3-dechloroethyl IF; 2-and 3-DCIIF) metabolites have a single chloroethylgroup at the endo-or exocylic nitrogen, respectively.

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