分子薬学および有機プロセス研究ジャーナル

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Determination of Intracellular Concentrations of Nucleoside Analogues and their Phosphorylated Metabolites

Lingli Mu, Xingling Liu, Sanwang Li, Fang Tang and Peng Yu

Nucleoside analogues are broadly used in antiviral and anti-tumor therapy. The clinical response depends on the intracellular formation of the pharmacologically active mono-, di-, and tri-phosphates moiety. So it is not advisable to simply monitore plasma concentration without concerning the variation of concentration of active constituent in some particular effector cell apparently while this kind of drugs are applied to the clinical therapy. Therefore, determination of intracellular concentration of nucleoside analogues and their phosphorylated metabolites is of great significance. In this review, several methods including RP-HPLC, LC-MS/MS, radioimmunoassay and capillary electrophoresis (CE) for analysis of nucleoside analogues are discussed. Because of the complex biological matrices as well as the extremely low concentration of target analytes, cell lysis techniques and sample pretreatment methods such as protein precipitation (PP) and solid-phase extraction (SPE) are also discussed.