Simultaneous Analysis of Fluoxetine, Norfluoxetine, Citalopram, and Haloperidol in Plasma by LC–ESI-IT-MS

A reliable and simple method has been developed for simultaneous analysis of fluoxetine, its metabolite norfluoxetine, citalopram, and haloperidol with lamotrigine as internal standard. The method is based on solid-phase extraction on mixed-mode cation-exchange cartridges followed by LC separation on a C18 column at ambient temperature with a gradient prepared from acetonitrile and 5 mM ammonium acetate in 0.1% (v/v) aqueous formic acid. The flow rate was 0.5 mL min−1. Eluted compounds were ionized by the electrospray ionization ion source of an ion-trap mass spectrometer and were detected by selected ion monitoring. Co-extracted endogenous compounds from plasma were eluted in the first 5 min and discarded by valve-switching. The target drugs were eluted in the period 5.5–11 min. Calibration plots were linear in the ranges 5 (or 10)–400 ng mL−1 with correlation coefficients >0.999. Other statistical and validation results were within accepted ranges for clinical analysis.