Jiří Beránek

Liquid chromatographic separation of purines, pyrimidines and their nucleosides on silica gel columns

Abstract The high-performance liquid chromatography of pyrimidine and purine derivatives on plain micropariculate silica gel was studied. Mixtures of dichloromethane, methanol and aqueous ammonium formate-formic acid solutions were used as the mobile phase. Retention data are reported for more than 50 compounds, including the biochemically important nucleobases and nucleosides. By varying the composition of the eluent mixture the chromatographic system provides elution sequences and slectivities that differ markedly from those characteristic of reversed-phase liquid chromatography.

Structure-intestinal transport and structure-metabolism correlations of some potential cancerostatic pyrimidine nucleosides in isolated rat jejunum

SummaryBoth transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2′-deoxyribonucleosides, and acetyl and 5′-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5′-Halogeno and 5′-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r=0.99, n=5).

The effect of structural modifications of 5-fluorouracil derivatives on their transport and biodegradation by isolated rat jejunum

SummaryThe continuous-perfusion technique was used in an isolated segment of everted rat jejunum to study transport and biotransformation processes in a series of cancerostatic derivatives of 5-fluorouracil. Metabolic alterations during penetration of the intestinal wall were assessed by high-performance liquid chromatography (HPLC). Octanol-buffer partition coefficients were measured, and the lipophilicity of the study compounds and fragmental constants for their sugar moieties were assessed. In the present series of 5-fluorouracil derivatives, there was no correlation between lipophilicity and metabolic cleavage to 5-fluorouracil, but a correlation was found between lipophilicity and the transport rate. Remarkable stability of the nucleoside bond and high biotransport were observed with 5′-chloro-5-fluorouridine, suggesting a different mode of activation for this derivative.