Liquid-phase microextraction for simultaneous chromatographic analysis of three antidepressant drugs in plasma

Abstract

A method using Liquid Phase Microextraction for simultaneous detection of citalopram (CIT), paroxetine (PAR) and fluoxetine (FLU), using venlafaxine as internal standard, in plasma by high performance liquid chromatography with fluorescence detection was developed. The linearity was evaluated between 5.0 and 500 ng mL-1 (r > 0.99) and the limit of quantification was 2.0, 3.0 and 5.0 ng mL-1 for CIT, PAR and FLU, respectively. Therefore, it can be applied to therapeutic drug monitoring, pharmacokinetics or bioavailability studies and its advantages are that it necessary relatively inexpensive equipment and sample preparation techniques. The SSRIs, citalopram (CIT), fluoxetine (FLU), fluvoxamine, paroxetine (PAR) and sertraline, are the result of research to find drugs as effective as TCAs, but with fewer problems with tolera- bility and safety. SSRIs inhibit serotonin reuptake potently and selectively, resulting in the increase of serotonergic neurotransmis- sion. Although they share the primary mechanism of action with TCAs, SSRIs are structurally distinct, with marked differences in the pharmacokinetic and pharmacodynamic profile. Sertraline and paroxetine are the most potent reuptake inhibitors. The relative potency of sertraline in inhibiting dopamine uptake differentiates it pharmacologically from other SSRIs. Citalopram and fluoxetine are racemic mixtures of chiral forms that have different pharmacokinetic and pharmacodynamic profiles. The fluoxetine metabolite is long acting and is pharmacologically active. SSRIs also have different pharmacokinetic profiles, including half-life, linear pharmacoki - netics versus the non-linear effect of age on its clearance, and its potential to inhibit the drug-metabolising isoenzyme, cytochrome P450 (CYP). These differences underscore that the pharmacological and pharmacokinetic clinical differences have become increasingly important for SSRIs.2 Figure 1 shows the chemical structures of