Roberto Mandrioli

Content of melatonin and other antioxidants in grape-related foodstuffs: measurement using a MEPS-HPLC-F method

Abstract:u2002 The strong antioxidant activity of melatonin is well known and it is important to investigate its presence and levels in different foodstuffs, for the purpose of evaluating their nutraceutical properties. As a contribution towards this goal, an original analytical method has been developed for the simultaneous determination of melatonin and other indolic and phenolic antioxidants (including trans‐ and cis‐resveratrol, ferulic acid, tryptophan, serotonin and 5‐hydroxyindoleacetic acid) in grape‐related foodstuffs and beverages: namely grape, grape juice, must, wine and grappa (Italian pomace brandy). These foodstuffs represent an important part of the diet, both traditionally and in recent times, especially in Mediterranean countries and could be (at least in part) responsible for the beneficial effects involved in the ‘French paradox’. The analytical method is based on high‐performance liquid chromatography coupled to fluorescence detection, exploiting the native fluorescence of the analytes. A C8 column was used as the stationary phase, while the mobile phase was composed of acidic phosphate buffer and acetonitrile; fluorescence intensity was monitored at λu2003=u2003386u2003nm while exciting at λu2003=u2003298u2003nm. The sample pretreatment was carried out by a fast and reliable microextraction by packed sorbent (MEPS) procedure. After validation, the method was applied to the analysis of melatonin and other antioxidants in food and beverages derived from grape, with very good results being obtained. Thus, this methodology may represent a promising tool for the evaluation of the antioxidant properties of nutraceuticals and functional foods.

Analysis of risperidone and 9-hydroxyrisperidone in human plasma, urine and saliva by MEPS-LC-UV

Risperidone is currently one of the most frequently prescribed atypical antipsychotic drugs; its main active metabolite 9-hydroxyrisperidone contributes significantly to the therapeutic effects observed. An original analytical method is presented for the simultaneous analysis of risperidone and the metabolite in plasma, urine and saliva by high-performance liquid chromatography coupled to an original sample pre-treatment procedure based on micro-extraction by packed sorbent (MEPS). The assays were carried out using a C8 reversed-phase column and a mobile phase composed of 73% (v/v) acidic phosphate buffer (30 mM, pH 3.0) containing 0.23% triethylamine and 27% (v/v) acetonitrile. The UV detector was set at 238 nm and diphenhydramine was used as the internal standard. The sample pre-treatment by MEPS was carried out on a C8 sorbent. The extraction yields values were higher than 92% for risperidone and 90% for 9-hydroxyrisperidone, with RSD for precision always lower than 7.9% for both analytes. Limit of quantification values in the different matrices were 4 ng/mL or lower for risperidone and 6 ng/mL or lower for the metabolite. The method was successfully applied to plasma, urine and saliva samples from psychotic patients undergoing therapy with risperidone, with satisfactory accuracy results (recovery>89%) and no interference from other drugs. Thus, the method seems to be suitable for the therapeutic drug monitoring of schizophrenic patients using the three different biological matrices plasma, urine and saliva.

Selective Serotonin Reuptake Inhibitors (SSRIs): Therapeutic Drug Monitoring and Pharmacological Interactions

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.

Dried blood spots: liquid chromatography-mass spectrometry analysis of Δ9-tetrahydrocannabinol and its main metabolites.

A sensitive and selective HPLC-MS/MS method has been developed for the first time for the analysis of Δ(9)-tetrahydrocannabinol (the most important active cannabinoid) and its hydroxylated and carboxylated metabolites in human Dried Blood Spots (DBSs). The simultaneous determination of Δ(9)-tetrahydrocannabinol and its two main metabolites allows assessing the time elapsed after the drug intake and distinguishing between acute or former consumption. This is an important information in specific contexts such as on street controls by police forces. DBSs have been chosen as the optimal biological matrix for this kind of testing, since they provide information on the actual state of intoxication, without storage and transportation problems usually associated with classical blood testing. The analysis is carried out on a C8 reversed phase column with a mobile phase composed of 0.1% formic acid in a water/methanol mixture and an electrospray ionisation (ESI) source, coupled to a triple quadrupole mass spectrometer. The method was validated according to international guidelines, with satisfactory results in terms of extraction yields, precision, stability and accuracy. Application to real DBS samples from Cannabis abusers gave reliable results, thus confirming the methodology suitability for roadside testing.

Monitoring of chronic Cannabis abuse: an LC-MS/MS method for hair analysis.

An advanced analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), has been developed for the identification and determination in hair of Δ(9)-tetrahydrocannabinol together with its major metabolite 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol. Since the latter is formed endogenously, it allows the assessment of chronic use excluding passive exposure to Cannabis. The sample pre-treatment procedure is based on a feasible incubative extraction followed by a liquid-liquid extraction step. Chromatographic separation was performed using a reversed-phase column and gradient elution with a formic acid/acetonitrile/water mobile phase. The limits of quantitation and of detection were 3pg/mg and 1pg/mg, respectively, for both analytes. The method was successfully applied to the analysis of hair samples from Cannabis abusers; the analyte concentrations found ranged from 55 to 100pg/mg for Δ(9)-tetrahydrocannabinol and from 5 to 10pg/mg for 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol. Accuracy studies also gave satisfactory results (recovery>87%), thus confirming the suitability of the assay for chronic consumption monitoring.

Recent trends in the analysis of amino acids in fruits and derived foodstuffs

AbstractThe amino acid content of fruit and fruit-derived foods is studied intensely because of the contribution to nutritional value, aroma, taste and health-promoting effects and their possible use as markers of origin and authenticity. In this review, based on 101 references, the most recent trends in the analysis of amino acids are presented: the most important techniques, the different sample treatment procedures (including derivatisation) and the most frequent applications are described and compared. Pertinent publications were retrieved from Scopus and Web of Knowledge database searches lastly performed in February 2012 with the keywords amino acid, analysis, liquid chromatography, gas chromatography, electrophoresis, fruit, and vegetables; the time limit was set from the year 2000 onwards. Although amino acids have been analysed in foods for decades, new technical possibilities and advancements have allowed ever-increasing accuracy and targeting of the methods in order to overcome the challenges posed by the complex plant matrices and their high intrinsic variability.n FigureAmino acid analysis in fruits

Fast analysis of amino acids in wine by capillary electrophoresis with laser-induced fluorescence detection

A fast analytical method has been developed for the determination of nine amino acids, together with serotonin, in wine samples of different origin and vintage. The method is based on capillary electrophoresis coupled to laser‐induced fluorescence detection. Separation was obtained by using a fused‐silica capillary (75u2009μm id, 74.0u2009cm total length, 60.0u2009cm length to detector) and a background electrolyte composed of carbonate buffer (20u2009mM, pH 9.2), applying a 20u2009kV voltage. Direct hydrodynamic injection of wine samples was made after an original microwave‐assisted derivatisation step with 5‐(4,6‐dichlorotriazinyl)aminofluorescein. Fluorescence was induced by an Ar‐Ion laser, exciting at 488u2009nm. Good linearity (r2>0.9990) was obtained for all considered analytes and sensitivity was also good, with limits of detection in the 7–50u2009ng/mL range. The method was successfully applied for the analysis of commercial Italian wines and thus seems to be suitable for the determination of the relevant amino acids and serotonin, providing good results in terms of accuracy and precision, together with the advantage of a very fast, microwave‐assisted derivatisation procedure. Future applications of the method are planned to check for wine adulterations and commercial frauds.

A fast and feasible microextraction by packed sorbent (MEPS) procedure for HPLC analysis of the atypical antipsychotic ziprasidone in human plasma

An original high-performance liquid chromatographic method coupled to microextraction by packed sorbent (MEPS) was developed for the therapeutic drug monitoring (TDM) of psychiatric patients treated with the recent atypical antipsychotic ziprasidone. The chromatographic separation was achieved on a RP C18 column, using an isocratic mobile phase and setting the wavelength at 320nm. The analyte was extracted from human plasma by means of a fast and feasible innovative MEPS procedure, optimised on C2 sorbent and requiring only 100μL of biological sample. A second pre-treatment procedure, based on solid phase extraction (SPE), has been also developed for comparison. The availability of different pre-treatment procedures allows the choice of the one best suiting the specific clinical, economic and scientific needs. The extraction yield values were always higher than 90% and sensitivity was also good, with a limit of quantitation (LOQ) of 1ng/mL. The method was successfully applied to plasma samples from ten subjects undergoing therapy with ziprasidone, thus confirming its suitability for the TDM of psychiatric patients, in order to personalise their pharmacological treatments.

Chiral analysis of amphetamines, methadone and metabolites in biological samples by electrodriven methods

Amphetamines and methadone are synthetic chiral drugs with a high potential for abuse. As such, several analytical methods have been developed for their enantioseparation and analysis in biological tissues, and some of these are based on electrodriven techniques. In this review, the most important and recent of these latter methods are reviewed and their main advantages and disadvantages are discussed. Particular attention is paid to the suitability of each method for the application to the biological matrix of interest: while all methods have been successfully applied for one or more biological tissues, to reach this goal they must overcome the sensitivity problem that is common to almost all capillary electrophoretic techniques. Most methods use one or more cyclodextrin derivatives as the chiral selector, thus the separation mechanism is not particularly complicated or unusual.

Evaluation of the pharmacokinetics, safety and clinical efficacy of sertraline used to treat social anxiety

Introduction: Social anxiety disorder (SAD) is an emerging, often invalidating, syndrome with deep personal, social and psychological implications. While multiple treatment strategies exist, presently none of them can be considered superior to all others. Areas covered: The aim of this review is to provide the latest information on sertraline (SRT), one of the most important selective serotonin reuptake inhibitors (SSRIs) currently used for the pharmacological therapy of SAD. A literature search was carried out with the keywords ‘sertraline, ‘social anxiety, ‘social phobia and ‘clinical trials. In this process, particular attention is paid to the pharmacokinetic characteristics of the drug and its safety in clinical use. Expert opinion: SRT is an effective drug in the treatment of SAD, especially when used in combination with some form of psychological support. While it does not seem to be significantly more effective than other SSRIs, SRT could offer some peculiar advantages: for example, it has a long half-life, allowing a single daily administration, and seems to be particularly indicated for the control of specific symptoms of SAD.