Biol. Pharm. Bull. 28(10) 2023—2025 (2005)

closely related major components of similar polarity and four polar hydrolysis products. The antimicrobial activities of these components against some microbial species are different. Pharmacokinetic studies in healthy volunteers have also shown that the plasma protein binding and volume of distribution of these teicoplanin components are different. Teicoplanin is highly bound to plasma proteins and low clearance, suggesting that the ratio of total and unbound concentrations in plasma may vary if protein binding changes. Although unbound teicoplanin is thought to be the active species, monitoring of plasma concentrations has been performed using total concentrations of drug. It needs to elucidate the relationship between unbound concentration and clinical efficacy, and the reason for the highly interindividual variations of total and unbound concentrations in plasma. FPIA is a widely used and very convenient method for determining the plasma concentration of teicoplanin. However, each component of teicoplanin cannot be determined separately and it is difficult to determine unbound concentrations in plasma because of detection limitations. Recently, Cociglio et al. reported validated coextractive cleanup techniques for two polar drugs, teicoplanin and ganciclovir. This approach appears to be simple and time-saving, but they determined only the main component of teicoplanin in their report and in preliminary studies we encountered some problems in applying their method to human plasma. In this study, we attempted to modify and improve this coextractive cleanup method and apply it to an isocratic HPLC procedure for quantitative determination of each teicoplanin component in plasma and ultrafiltered plasma.