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New-generation antidepressants are a heterogeneous class of drugs used in the treatment of depression and related disorders. This review deals with the first new-generation antidepressant class to enter the pharmaceutical market, i.e., selective serotonin reuptake inhibitors (SSRIs), which are still the most prescribed and widely used ones. Their common characteristics are the comparable clinical efficacy, good tolerability and relative safety in comparison to “first generation antidepressants”, i.e. classic tricyclic antidepressants and monoamine oxidase inhibitors. This class of drugs includes fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and, since 2011, vilazodone. In this review, the main pharmacodynamic and pharmacokinetic properties of the six commercially available SSRIs are described, focusing on side and toxic effects, chemical-clinical correlations, interactions with other drugs, the role of therapeutic drug monitoring (TDM) and related bioanalytical methodologies.

A review with 103 references. Fluoxetine is the parent drug of the SSRI (selective serotonin reuptake inhibitor) antidepressant class, and is still one of the most highly used drugs of this class world-wide. Fluoxetine now has largely (albeit not completely) substituted older and less safe drugs such as tricyclic antidepressants. Different cytochrome P450 isoforms are involved in the metabolism of fluoxetine, however, the main active metabolite, norfluoxetine, is produced by the CYP2D6 action in the human liver. In this paper, the main metabolic characteristics of fluoxetine will be reviewed, with particular attention paid to the role of cytochrome isozymes. The pharmacological interactions of the drug will be overviewed, especially those concerning other drugs used in psychiatric clinics, such as antipsychotics and antidepressants and the relationships between pharmacological interactions and cytochrome activity will be discussed. Recently, much attention has been drawn to the therapeutic drug monitoring (TDM) of fluoxetine, and in particular to the analysis of fluoxetine enantiomers for which enantiomeric separations and enantioselective metabolism will also briefly be mentioned.

The introduction in clinical practice of new antipsychotic drugs neurologically safer and with a broader spectrum of efficacy than “classical” neuroleptics has brought about significant improvement in the therapy of schizophrenic patients. These second-generation antipsychotics usually called “atypical” antipsychotics, have several therapeutical features in common, such as their effectiveness against the negative symptoms of schizophrenia and the advantage of not causing severe extrapyramidal symptoms and hyperprolactinemia. The therapeutic drug monitoring of patients treated with atypical antipsychotics is however, still advisable. In many cases, it can avoid the onset of side and toxic effects due to high plasma levels of the drug caused by overdose or interactions with other drugs. Furthermore, monitoring can significantly improve the patient's compliance, thus leading to higher treatment efficacy. The pharmacological properties of the most widely used atypical antipsychotics (clozapine, olanzapine, risperidone and quetiapine) will be treated herein with particular attention paid to metabolism, side effects and pharmacokinetics. The analytical methods suitable for the therapeutical drug monitoring of these drugs will also be discussed, in terms of sensitivity, selectivity and usefulness in clinical settings. Other recent atypical agents (ziprasidone, aripiprazole, iloperidone, sertindole and zotepine) will be described as well.

A simple and sensitive HPLC method is proposed for the determination of glutathione (GSH) in human mononuclear cells, based on the derivatization of the tripeptide with Ellman’s reagent. The mobile phase was composed of a mixture of methanol and ammonium formate (10:90 v/v, with a flow rate of 1 mL/min). The stationary phase was a C18 (4.6 μm, 250 × 4 mm) reversed phase column. The detection of GSH was performed at 280 nm, resulting in a neat chromatographic peak at 5.8 min. A calibration curve showed good linearity over the concentration range 3 × 10⁻⁶– 6 × 10⁻⁵ M, with a satisfactory precision. The method was found to yield a quantitative recovery of glutathione (96%), to be sensitive (down to 30 pmol of glutathione per injection) and to have a high precision (R.S.D.% ≅ 2). The proposed HPLC method allows for the separation and quantitation of cysteine and N-acetylcysteine, if present in biological samples. Furthermore, the method allows for the determination of total thiol present in human mononuclear cells. © 1998 John Wiley & Sons, Ltd.

Fluoxetine is an atypical antidepressant drug, which selectively inhibits the neuronal reuptake of serotonin, and is widely used in the treatment of depressive disorders. The aim of this research is the development of an HPLC method with fluorescence detection for the monitoring of fluoxetine plasma levels. The determination requires no more than 250 μl of plasma, which undergo solid phase extraction (SPE), then are injected in the HPLC. For the analytical separation a reversed phase C8 column (150×4.6 mm I.D.) was used, while the mobile phase was a mixture of acetonitrile and water containing perchloric acid and tetramethylammonium perchlorate (flow rate: 1 ml min−1). The very low levels of analytes in plasma required the employment of a fluorescence detector (λexc=230 nm, λem=290 nm), which also granted a good selectivity. Fluoxetine is revealed as a single peak at a retention time of 9.7 min, while norfluoxetine, the main metabolite of fluoxetine, is revealed at a retention time of 8.1 min. Linearity was obtained over the concentration range 8–200 ng ml−1for both substances. The method seems suitable, in accuracy and precision, for the determination of fluoxetine plasma levels of patients; furthermore, it is rapid and sensitive.

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Retroperitoneal cystic lymphangioma is a benign, endothelium-lined, cystic tumour of the lymphatic system. The tumour may be unilocular or composed of large cyst-like cavities filled with a clear, watery or serous fluid. It is more commonly seen in the neck, where it is called a cystic hygroma, and is relatively rare in the retroperitoneal area. It has been suggested that congenital or developmental misplacement and obliteration of draining lymphatics may lead to proximal cystic dilatation and the formation of these lymphangiomas; Some cysts may be due to other factors, such as trauma, resulting in lymphatic effusion and encapsulation, or to an acquired lymphatic obstruction.A 56-year-old man presented with a 10 cm deep, fixed abdominal mass in the left paramedian position below the level of the umbilicus. The mass was soft, cystic and painless on palpation. Echotomography showed a large, echo-free, smooth, cyst-like mass in the left paravertebral region (Fig. 1). This appearance was considered to be compatible with either a retroperitoneal cystic mass or a localized lymphoma. Subsequent lymphography showed an interruption of the left paraaortic lymphatic channels on the immediate post-injection fikns. The 24 h films showed a mass outlined by the lymphographic contrast medium which had presumably penetrated the cystic cavity and had become localized on the internal wall of the cyst (Fig. 2). These appearances suggested a large lymphatic cyst—the result of interruption of the para-aortic lymphatic channels.

A sensitive and accurate method for the spectrofluorimetric determination of trace levels of aluminum in hemodialysis solutions using Mordant Red 19 as the complexation reagent has been developed. The optimal experimental conditions for the concentration of fluorimetric reagent, pH, temperature, and the specific type of matrix are reported. The emission of the fluorescent metal chelate was measured at 555 nm, excitation at 478 nm. Linearity between emission intensity and aluminum concentration was found in the 2–20 ppb range in standard aluminum solutions. Limit of detection was 0.4 ppb. The aluminum amounts in some commercial hemodialysis solutions were determined by means of the extrapolation method. The proposed method proved to be suitable in terms of sensitivity and accuracy for the determination of aluminum in dialysis fluids.