Liquid chromatographic separation of phosphoramidate diastereomers on a polysaccharide-type chiral stationary phase
| Autor: | Philippe Morin, Nathalie Mesplet, Yoshio Saito, Luigi A. Agrofoglio |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Detection limit
Electrospray Spectrometry Mass Electrospray Ionization Chromatography Organic Chemistry Diastereomer Reproducibility of Results Phosphoramidate Stereoisomerism General Medicine Prodrug Biochemistry High-performance liquid chromatography Amides Sensitivity and Specificity Analytical Chemistry chemistry.chemical_compound chemistry Dideoxynucleotide Polysaccharides Phosphoric Acids Enantiomer Chromatography High Pressure Liquid |
| Zdroj: | Journal of chromatography. A. 983(1-2) |
| ISSN: | 0021-9673 |
| Popis: | To improve the therapeutic potential of anti-HIV nucleoside analogues (d4T, AZT, 3TC and ddI), the delivery of the corresponding monophosphate from neutral, membrane-permeable prodrugs has been realised by the synthesis of lipophilic phosphoramidate triester prodrugs, such as the simple phenyl- l -alaninephosphate derivatives. However, the present non-stereoselective synthesis results in a mixture of 1:1 diastereomers, which differ from the configuration of the phosphorus atom asymmetric center. Since each diastereomer may have different biological activity and pharmacokinetic profile, analytical methods have to be developed for their separation. This work aims at showing the ability of a polysaccharide-type chiral stationary phase to resolve such diastereomers in reversed-phase high-performance liquid chromatography. The influence of operating parameters has been studied to optimise the separation; a thermodynamic approach has also been investigated to gain an insight in the retention mechanism of the prodrugs. Preliminary validation study (linearity, accuracy, repeatability) has yielded good results; in addition, the feasibility of HPLC–electrospray-mass spectrometry (HPLC–ESI-MS) coupling has been demonstrated and it is expected that this will lead to lower detection limits. |
| Databáze: | OpenAIRE |
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