Biomedical subjects

M A Raggi

Publications and source records attributed to M A Raggi.

At least 19 recordsLinked to original sources

PubMed2006

Determination of homovanillic acid (HVA) in human plasma by HPLC with coulometric detection and a new SPE procedure.

A sensitive high-performance liquid chromatographic method has been developed for the determination of homovanillic acid (HVA), the main metabolite of dopamine, in human plasma. Analyses were carried out on a reversed-phase column (C8, 250 mm x 4.6 mm i.d., 5 microm) using a mobile phase composed of 10% methanol and 90% aqueous citrate buffer, containing octanesulfonic acid and EDTA at pH 4.8. Coulometric detection was used, setting the guard cell at +0.100 V, the first analytical cell at -0.200 V and the second analytical cell at +0.500 V. A careful solid-phase extraction procedure, based on strong anion exchange (SAX) cartridges (100 mg, 1 mL), was implemented for the pre-treatment of plasma samples. Extraction yield was satisfactory, being the mean value 98.0%. The calibration curve was linear over the concentration range of 0.2-25.0 ng mL(-1) of homovanillic acid. The limit of quantitation (LOQ) was 0.2 ng mL(-1) and the limit of detection (LOD) was 0.1 ng mL(-1). The method was successfully applied to plasma samples from former alcohol, cocaine and heroin addicts. Results were satisfactory in terms of precision and accuracy. Hence, the method is suitable for the determination of homovanillic acid in human plasma.

Calibration↗

PubMed2006

Fluoxetine metabolism and pharmacological interactions: the role of cytochrome p450.

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.

Animals↗

PubMed2005

Capillary electrophoretic analysis of the antibiotic vancomycin in innovative microparticles and in commercial formulations.

A new fast capillary electrophoretic method has been developed for the analysis of the glycopeptide antibiotic vancomycin in formulations. An electrophoretic run is completed within 3.0 min; fused silica capillaries (100 microm i.d., 8.5 cm effective length and 48.5 cm total length) and a background electrolyte consisting of 12.5 mM, pH 2.5 phosphate buffer are used. The applied voltage is -20.0 kV; samples are injected by pressure (30 mbar x 3 s) at the anodic end of the capillary. The method was successfully applied to innovative controlled release microparticles consisting of a coated albumin core containing vancomycin. A simple procedure has been developed to obtain complete vancomycin extraction from microparticles using a 5% (w/v) sodium dodecyl sulphate aqueous solution. The method has been validated in terms of linearity, precision and accuracy. Good linearity was found in the 0.25-5.00 microg/mL range. Satisfactory precision was obtained, with relative standard deviation values always lower than 3.9%; accuracy was satisfactory, with recovery values between 97.8 and 102.2%. The method is also suitable for vancomycin determination in commercial capsules.

Anti-Bacterial Agents↗

PubMed2005

Vitamin C content and antioxidant activity of the fruit and of the Ayurvedic preparation of Emblica officinalis Gaertn.

Emblica officinalis Gaertn. is one of the most important plants of Ayurved, the traditional Indian medicine. In this ancient medicine, the fruit of Emblica officinalis is processed according to a method named "Svaras Bhavana", whereby the therapeutic potential of the plant is enhanced by treating the main herb with its own juice. For many years, the activity of the fruits was attributed to the high content of ascorbic acid; however, this has recently been questioned. The aim of the paper is to clarify this matter. A reliable and feasible HPLC method with diode array detection has been developed for the determination of ascorbic acid in Emblica fruit and particularly in Emblica fruit processed according to the Ayurvedic method. The antioxidant effects have also been evaluated in comparison to the real levels of Vitamin C by different antioxidant tests. The data obtained show that the Emblica fruit contains ascorbic acid (0.4%, w/w), and that the Ayurvedic method of processing increases the healthy characteristics of the fruit thanks to a higher antioxidant activity and a higher content of ascorbic acid (1.28%, w/w). It has also been found that Vitamin C accounts for approximately 45-70% of the antioxidant activity.

Antioxidants↗

PubMed2003

Neuroendocrine responses to experimentally-induced emotions among abstinent opioid-dependent subjects.

The present study investigated neuroendocrine and cardiovascular changes during experimentally-induced affective states in abstinent heroin-dependent subjects and healthy controls. The procedure for eliciting emotions in all subjects used pleasant and unpleasant stimuli that did not differ in subjective arousal properties. We investigated whether the valence of the stimuli differentially affected neuroendocrine responses by comparing neutral, pleasant and unpleasant pictures on heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), methyl-OH-phenyl-glycol (MHPG), norepinephrine (NE), epinephrine (EPI), adrenocorticotrophic hormone (ACTH) and cortisol (CORT) plasma levels. Twelve abstinent heroin-dependent subjects, in comparison with 12 control subjects, were submitted to three experimental sessions, each on one of three experimental days a week apart, in counterbalanced order: day 1=unpleasant pictures, day 2=pleasant pictures, day 3=neutral pictures. In the rating of subjective arousal pleasant and unpleasant stimuli received the same high score in comparison with neutral stimuli; a different cardiovascular and neuroendocrine pattern was obtained in healthy subjects: unpleasant stimuli elicited increases in HR, SBP, MHPG, NE, ACTH, CORT, whereas neutral and pleasant stimuli did not induce any significant response in hormonal levels. In contrast, in heroin addicts, despite increased perceptions of unpleasantness, HR, SBP, MHPG and NE levels did not increase after disliked stimuli; these subjects also reported increased arousal during exposure to neutral stimuli. In comparison with controls, addicted individuals showed higher CORT and ACTH basal levels, and a consequent lack of response to unpleasant stimuli. The results indicate that neuroendocrine and cardiovascular systems respond selectively to affective, motivationally relevant stimuli, and that substance use disorders may be associated with dysregulation of emotion-processing mechanisms.

Adrenocorticotropic Hormone↗

PubMed2003

Liquid chromatographic determination of oxcarbazepine and its metabolites in plasma of epileptic patients after solid-phase extraction.

A method based on high-performance liquid chromatography with UV detection in combination with solid-phase extraction for sample pretreatment has been developed for the simultaneous analysis of the antiepileptic drug oxcarbazepine and its main metabolites in human plasma. The extraction of the analytes from plasma samples was carried out by means of a selective solid-phase extraction procedure using hydrophilic-lipophilic balance cartridges. The separation was obtained on a reversed-phase column (C(18), 150x4.6 mm I.D., 5 micrometer) using a phosphate buffer-acetonitrile-methanol-triethylamine mixture (final apparent pH* 3.5) as the mobile phase. Under these chromatographic conditions, oxcarbazepine and its metabolites 10,11-dihydro-10-hydroxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine and the internal standard are baseline separated in less than 9 min. The extraction yield values were >94% for all analytes and the precision, expressed by the RSD%, was in the low percentage range. For the entire method, including sample pre-treatment and HPLC determination, the linearity of the calibration lines, expressed by the linear correlation coefficient, was better than 0.995; the limit of quantitation was 15 ng ml(-1). The method was applied to plasma samples from patients undergoing chronic treatment with oxcarbazepine, both in monotherapy and in polytherapy. Based on the analytical parameters precision, accuracy, limit of quantitation and analysis time the method is suitable for routine application in therapeutic drug monitoring.

Anticonvulsants↗

PubMed2002

HPLC analysis of the novel antipsychotic drug quetiapine in human plasma.

A precise and feasible high-performance liquid chromatographic (HPLC) method for the analysis of the novel antipsychotic drug quetiapine in plasma has been developed. The analysis was carried out on a C8 (150x4.6 mm i.d., 5 micrometer) reversed-phase column, using a mixture of acetonitrile, methanol and pH 1.9 phosphate buffer as the mobile phase; triprolidine was used as the internal standard. Careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE). A good linearity was found in the 4-400 ng ml(-1) quetiapine plasma concentration range. The application to some plasma samples of patients treated with Seroquel(R) tablets gave satisfactory results. The accuracy was good (quetiapine mean recovery=92%), as well as the precision (mean RSD=3.3%). The method seems to be suitable for the clinical monitoring of patients treated with quetiapine.

Antipsychotic Agents↗

PubMed2002

Rapid methods for determination of fluoxetine in pharmaceutical formulations.

Two different analytical methods for the quality control of fluoxetine in commercial formulations have been developed and compared: a spectrofluorimetric method and a capillary zone electrophoretic (CZE) method. The fluorescence emission values were measured at lambda=293 nm when exciting at lambda=230 nm. The CZE method used an uncoated fused-silica capillary and pH 2.5 phosphate buffer as the background electrolyte. The extraction of fluoxetine from the capsules consisted of a simple one-step dissolution with methanol/water, filtration and dilution. Both methods gave satisfactory results in terms of precision; the best results were obtained for the electrophoretic method, with RSD% values always lower than 2.0%. The accuracy was assessed by means of recovery studies, which gave very good results, between 97.5 and 102.6%. Furthermore, both methods also have the advantage of being very rapid.

Capsules↗

PubMed2002

Analysis of reboxetine, a novel antidepressant drug, in pharmaceutical tablets by capillary electrophoresis and derivative spectrophotometry.

The recent antidepressant drug reboxetine was quantified in pharmaceutical tablets by derivative spectrophotometry and capillary zone electrophoresis. The feasible sample pretreatment consists of a single extraction with a pH 2.5 phosphate buffer, centrifugation and dilution. For the spectrophotometric assay, the fourth derivative of the absorbance was used which gave satisfactory results in terms of accuracy (mean recovery 99.7%) and precision (mean RSD 3.4%). The electrophoretic experiments were carried out using the shortest effective length of the capillary (8.5 cm) in order to obtain a very rapid separation of reboxetine and dibenzepine used as the internal standard. Using a pH 2.5, 50 mM phosphate buffer as the background electrolyte, each analysis lasted less than 2.5 min. Accuracy (101.3%) and precision (1.5%) were very good.

Antidepressive Agents↗

PubMed2002

Therapeutic drug monitoring: chemical-clinical correlations of atypical antipsychotic drugs.

In the last few years, new drugs for the treatment of schizophrenia have been introduced in therapy which have noticeably improved the quality of life of many schizophrenic patients. These new "atypical" drugs have chemical, pharmacological and clinical properties which are different from those of the classical neuroleptics. The most used drugs among the "atypical" antipsychotics are clozapine, olanzapine, quetiapine and risperidone. Despite several differences in their pharmacokinetic and pharmacodynamic profiles, they show some common properties: e.g. they don't cause extrapyramidal side effects, and they are active against the negative as well as positive symptoms of schizophrenia. The need for clinical monitoring of patients undergoing therapy is still evident because the onset of side effects is often related to high plasma concentrations of the drug. The clinical monitoring of patients can significantly improve the knowledge of pharmacological interactions among different CNS drugs, as well as enhance the compliance of the patients, thus leading to higher treatment efficacy. In order to carry out efficient clinical monitoring, reliable analytical methods are needed to determine the analytes even at very low concentrations and in the presence of other drugs. For this purpose, analytical techniques such as gas or liquid chromatography are often used coupled with sensitive and selective means of detection, such as fluorimetric, electrochemical or mass spectrometry detectors. The most recent studies on the determination of atypical antipsychotics will be reviewed in addition to the issue of sample pretreatment which is a critical step when the analysis of biological fluids is concerned.

Antipsychotic Agents↗

PubMed2001

Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates.

Objective measures of experimentally-induced aggressiveness were evaluated in 20 methadone-treated heroin addicts, in comparison to 20 normal healthy male subjects. All the subjects were submitted to preliminary DSM IV interviews, Buss Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the point subtraction aggression paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money, which was attributed to a fictitious other participants. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response), or protecting their counter (escape response). Money-earning responses were significantly lower (t=4.38, P<0.001) and aggressive responses significantly higher (t=5.45; P<0.001) in methadone patients in comparison to controls. During the experimentally-induced aggressiveness, plasma adrenocorticotropic hormone (ACTH), cortisol (CORT) and growth hormone (GH) concentrations increased significantly less and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), significantly more in methadone subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between methadone doses, or exposure extent, and aggressiveness levels. Our findings suggest that heroin dependent patients have higher outward-directed aggressiveness than healthy subjects, in relationship with monoamines hyper-reactivity, also under methadone medication. Aggressiveness in methadone patients seems to be related more to the personality traits than to drug effects. Hypothalamus-pituitary-adrenal (HPA) axis responses, unexpectedly dissociated from catecholamines rise among methadone patients, could be due to a long-lasting inhibitory action exerted by opiates on pro-opio-melanocortin (POMC), or to a premorbid psychobiological condition that exhausted hormonal reactivity.

Adult↗

PubMed2001

Rapid capillary electrophoretic method for the determination of clozapine and desmethylclozapine in human plasma.

A rapid and sensitive high-performance capillary electrophoretic method for the determination of clozapine and its main metabolite desmethylclozapine in human plasma was developed. The separation of the two analytes was carried out in an untreated fused-silica capillary [33 cm (8.5 cm effective length) x 50 microm I.D.] filled with a background electrolyte at pH 2.5 containing beta-cyclodextrin. Baseline separation of clozapine and desmethylclozapine was recorded in less than 3 min. An accurate sample pretreatment by means of solid-phase extraction and subsequent concentration allows for reliable quantitation of clozapine in the plasma of schizophrenic patients under treatment with the drug. The method showed good precision (mean RSD = 4.0%) as well as satisfactory extraction yields (approximately 88%) and a good sensitivity (limit of quantitation = 0.075 microg ml(-1), limit of detection = 0.025 microg ml(-1)).

Antipsychotic Agents↗

PubMed2001

Separation of olanzapine, carbamazepine and their main metabolites by capillary electrophoresis with pseudo-stationary phases.

Conditions were worked out for the separation of carbamazepine, olanzapine, and their main metabolites carbamazepine 10,11-epoxide, 10-hydroxycarbamazepine, and desmethylolanzapine. The separation was based on electrokinetically driven methods in the capillary format. The main difficulty in separating these compounds is related to their different chemical classes. Whereas the carbamazepine members are amides, and are electrically neutral, the olanzapine members have aliphatic amino groups and are thus cationic under most experimental conditions. Different additives were applied as pseudo-stationary phases to implement selectivity. Poly(diallyldimethylammonium), PDADMA, is a polycationic replaceable and soluble polymer, that interacts mainly according to the polarisability of the analyte molecules. The MEKC principle was applied with the common SDS as micelle former. In both systems, only partial resolution of the analytes was obtained. The most favorable system consisted of a charged, oligomeric additive: full separation of all analytes within 4 min was achieved with heptakis-6-sulfato-beta-cyclodextrin (7 mM) in 30 mM borate buffer, pH 8.5.

Antipsychotic Agents↗

PubMed2001

A sensitive high-performance liquid chromatographic method using electrochemical detection for the analysis of olanzapine and desmethylolanzapine in plasma of schizophrenic patients using a new solid-phase extraction procedure.

A high-performance liquid chromatographic method with amperometric detection for the analysis of the novel antipsychotic drug olanzapine and its metabolite desmethylolanzapine in human plasma has been developed. The analysis was carried out on a reversed-phase column (C8, 150 x 4.6 mm I.D., 5 microm) using acetonitrile-phosphate buffer, pH 3.8, as the mobile phase. The detection voltage was + 800 mV and the cell and column temperature was 30 degrees C. The flow-rate was 1.2 ml min(-1). Linear responses were obtained between 5 and 150 ng ml(-1), with repeatability <3.3%. A careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE) on C8 cartridges. The method requires 500 microl of plasma for one complete analysis. Absolute recovery exceeded 97% for both olanzapine and desmethylolanzapine, and the detection limit was 1 ng ml(-1) for both analytes. Repeatability, intermediate precision and accuracy were satisfactory. This sensitive and selective method has been successfully applied to therapeutic drug monitoring in schizophrenic patients treated with Zyprexa tablets.

Antipsychotic Agents↗

PubMed2001

Pivagabine effects on neuroendocrine responses to experimentally-induced psychological stress in humans.

Neuroendocrinology of chronic stress seems to be characterized by HPA axis hyperactivity and early childhood stressors have been hypothesized to predispose individuals to adult onset depression by means of dysregulation of the HPA axis. Pivagabine (PVG), a hydrophobic 4-aminobutyric acid derivative, has been used experimentally recently in the treatment of different disorders related to stress-maladaptation, because of its possible inhibitory action on corticotrophin releasing factor secretion and HPA axis function. In the present study, 20 healthy male subjects were each exposed twice to the same psychosocial stressor (stroop color-word interference task, public speaking and mental arithmetic in front of an audience) during a first session (day 1) and a second session (day 8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH) and cortisol (CORT), heart rate (HR) and systolic blood pressure (SBP) were measured immediately before the beginning of the tests and at their end, 30 min later, on both experimental days. Utilizing a double blind schedule, the subjects received pivagabine (900 mg, twice a day)(PVG group: nine subjects) or placebo (PBO group: 11 subjects) during the 7 days between the two stress sessions. NE, EPI, ACTH, and CORT levels were significantly elevated after stress exposure on day 1 and day 8 in PBO group subjects. After PVG treatment, on day 8, ACTH, CORT, NE and EPI responses to stress were significantly blunted, together with HR and SBP, in PVG group subjects. These results add to the evidence concerning PVG capacity to inhibit the HPA axis in humans, in response to stressful stimuli, and suggest that the action of PVG may be mediated not only by GABAergic receptors, but also by the suppression of catecholamines response. PVG treatment could modulate HPA hyper-responsiveness to stress in subjects with negative affectivity and depressive traits.

Adrenocorticotropic Hormone↗

PubMed2001

Neuroendocrine responses to experimentally-induced psychological stress in healthy humans.

Previous studies of hormonal and neurophysiological changes in response to psychological stress in humans have produced contrasting findings due to differing experimental procedures and consistent individual variability. Habituation effects, which influence physiological coping in response to exposure to repeated stress, need to be investigated more extensively. In the present study, twenty healthy male subjects were each exposed twice to the same psychosocial stressor (Stroop Color Word Interference task, public speaking and mental arithmetic in front of an audience) during a first session (day 1) and a second session (day 8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), cortisol (CORT) and prolactin (PRL) were measured immediately before the beginning of the tests and at their end, 30 min later, on both experimental days. For the total group, NE, EPI, ACTH, and CORT levels were significantly elevated, and PRL levels were significantly decreased, after stress exposure on day 1. ACTH and CORT levels showed less significant increases after stress on day 8. In contrast, NE and EPI responses to stress were not significantly blunted, and PRL response was unchanged on day 8. Cluster analysis revealed two groups of subjects who showed different habituation patterns for ACTH and CORT. The first group (n=12) of subjects showed a reduction of ACTH and CORT responses to stress on day 8. The subjects of the second group (n=8) displayed a significant increase of ACTH and cortisol in response to stress on day 8, without any habituation effect. These results increase the evidence concerning the involvement of the HPA axis and catecholamines in response to psychological stress, and suggest that possible individual differences in the neuroendocrine coping mechanisms may affect mood regulation and the state of health.

Adrenocorticotropic Hormone↗

PubMed2001

Experimentally induced aggressive behavior in subjects with 3,4-methylenedioxy-methamphetamine ("Ecstasy") use history: psychobiological correlates.

PURPOSE: Objective measures of experimentally induced aggressiveness were evaluated in 12 male 3,4-methylenedioxy-methamphetamine (MDMA, "Ecstasy") users, in comparison with 20 healthy male subjects. METHODS: All the subjects were preliminarily submitted to DSM-IV interviews and Buss-Durkee Hostility Inventory (BDHI). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money that was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Escape responses were also possible protecting the counter from monetary subtractions. RESULTS: Money-earning responses were not different in Ecstasy users and controls; aggressive responses were significantly higher in Ecstasy users in comparison with control subjects (F=20.74, P<.001). Baseline adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels were higher in Ecstasy users than in controls. No difference was found in norepinephrine (NE) and epinephrine (EPI) basal levels of the two groups. During the experimentally induced aggressiveness, plasma ACTH concentrations increased significantly less and NE and EPI levels, together with heart rate (HR), increased significantly more in Ecstasy users than in healthy subjects. Despite ACTH-blunted responses, CORT did not increase differently from controls in Ecstasy users. PSAP aggressive responses positively correlated with catecholamines and CORT changes, BDHI Direct Aggression and Irritability scores, both in Ecstasy users and controls. A significant correlation was found between Ecstasy exposure extent and aggressive responses (r=.78, P<.001). IMPLICATIONS: Our findings suggest that Ecstasy users have higher outward-directed aggressiveness than healthy subjects. Aggressiveness in MDMA subjects seems to be associated more with MDMA pharmacological effects than with personality traits: Nevertheless, a premorbid psychobiological proneness to aggressive behavior cannot be excluded. Increased catecholamines reactivity, basal hypothalamus-pituitary-adrenal (HPA) axis hyperactivity, and blunted ACTH responses could be due to MDMA action on monoaminergic pathways and adrenal function.

Adolescent↗

PubMed2000

A rapid LC method for the identification and determination of CNS drugs in pharmaceutical formulations.

Antidepressant, neuroleptic and antiepileptic drugs were identified and determined in pharmaceutical formulations (tablets, capsules and oral solutions) by a rapid high-performance liquid chromatography method. The sample pretreatment consisted of a one-step extraction, filtration and dilution. The chromatographic conditions were: reversed-phase C8 column (150 x 4.6 mm i.d., 5 microm); acetonitrile-tetramethylammonium perchlorate aqueous solution (pH 2.8; 12.6 mM) (45:55, v/v) as the mobile phase; detection wavelength, 230 nm. Calibration curves were linear in the 100-1000 ng ml(-1) range for all tested drugs except for phenobarbital. The repeatability (or intra-day precision), expressed by the relative standard deviation, was better than 2.0%. The accuracy, resulting from recovery studies, was between 98.1 and 101.3%. The amount of drug found agreed with the declared content within the limits specified by United States Pharmacopeia and British Pharmacopeia.

Calibration↗