Melitracen and the internal standard (I.S.), trifluoperazine, were extracted from plasma by a convenient liquid-liquid extraction. Chromatographic separation was performed on a Thermo Hypersil-Hypurity C18 with the mobile phase consisting of 10 mM ammonium acetate–methanol–acetonitrile. A single-quadrupole mass spectrometer with an electrospray interface was operated in the selected-ion monitoring mode to detect the [M + H]+ ions at 292 m/z for melitracen and 408 m/z for trifluoperazine. The method was validated over 0.4–50.0 ng mL−1 for melitracen. The recovery was 73.52–78.91%, and the lower limit of quantitation (LLOQ) detection was 0.4 ng mL−1 for melitracen. The intra- and inter-day precision of the method at three concentrations were 2.96–7.76% with accuracy of 95.75–100.48%. Stability of compounds was established in a battery of stability studies. The bioequivalence of melitracen in the two formulations was evaluated in 18 healthy Chinese male volunteers with this assay. The described method showed acceptable precision, accuracy, linearity, stability, specificity and can be widely used for pharmacokinetic studies, and routine therapeutic drug monitoring.
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