Simultaneous high-performance liquid chromatographic determination of quinupristin, dalfopristin and their main metabolites in human plasma

Quinupristin–dalfopristin (30:70, w/w) is a new streptogramin, which has been developed for intravenous use. A specific and sensitive HPLC method was developed to measure simultaneously quinupristin (RP 57669) and dalfopristin (RP 54476) and their main metabolites in human plasma. The metabolites measured by this method were RP 69012 (glutathione-conjugated) and RPR 100391 (cysteine-conjugated) from quinupristin and RP 12536 (natural pristinamycin IIA), from dalfopristin. Solid-phase extraction with disposable cartridges was combined with reversed-phase HPLC and fluorimetric detection for RP 57669, RP 69012 and RPR 100391 and UV detection for RP 54476 and RP 12536. The method provided good recovery and low limits of quantitation (0.025 mg l⁻¹ for RP 57669, RP 54476 and RP 12536, and of 0.010 mg l⁻¹ for RP 69012 and RPR 100391). The validated range of concentrations of the method was: 0.025–5000 mg l⁻¹ for RP 57669, RP 54476 and RP 12536 and 0.010–0.750 mg l⁻¹ for RP 69012 and RPR 100391.