Preparative and analytical high-performance liquid chromatographic methods in the synthesis and analysis of decomposition of nitrosourea nucleosides.
Details are given for reversed-phase, adsorption, and aqueous ammonia-modified adsorption high-performance liquid chromatographic systems developed to separate 3'-chloroethylnitrosourea analogues of thymidine, 2'-deoxyuridine, and 5-fluoro-2'-deoxyuridine from their decomposition products and synthetic precursors. The effect of varying the substituent at the 3'- and 5-position on relative retention in each system is discussed. These systems are used to purify intermediates in the synthesis of these potent antineoplastic agents, and for the simultaneous analysis of the nitrosourea nucleosides and their breakdown products in kinetic studies of their decomposition. Application of these methods to the analysis of the kinetics of the breakdown of these compounds is demonstrated, with detection limits (signal-to-noise ratio = 2) in the 1-2 ng range.
D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007700:Kinetics; D009607:Nitrosourea Compounds / Q000032:analysis* / Q000138:chemical synthesis; D009705:Nucleosides / Q000032:analysis* / Q000138:chemical synthesis; D011743:Pyrimidines
D009607:Nitrosourea Compounds; D009705:Nucleosides; D011743:Pyrimidines