PubMed Health⌕ Search

Biomedical subjects

M A Raggi

Publications and source records attributed to M A Raggi.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed2000

Quality control of benserazide-levodopa and carbidopa-levodopa tablets by capillary zone electrophoresis.

In modern practice, the treatment of Parkinson's disease and syndrome is carried out using pharmaceutical formulations containing a combination of levodopa and a decarboxylation inhibitor (carbidopa or benserazide). Two pharmaceutical formulations were quantified by capillary zone electrophoresis using two procedures which differed only in the kind of background electrolyte used. One procedure used a 25 mM phosphate buffer, pH 2.5, while the second one used a 25 mM borate buffer, pH 8.5. The electrophoretic analysis was carried out using an uncoated fused- silica capillary, a separation voltage of 20 kV with currents typically less than 60 microA, and spectrophotometric detection at 205 nm. Calibration curves were performed for levodopa (concentration range 1-100 microg/mL), for carbidopa and benserazide (1-50 microg/mL), and the plots of the peak area versus concentration were found to be linear with a correlation coefficient better than 0.9990. Satisfactory results were obtained when commercial tablets were analyzed in terms of accuracy (98-102%), repeatability (0.6-2.0%), and intermediate precision (1.1-2.6%).

Benserazide↗
PubMed2000

Quantitation of olanzapine in tablets by HPLC, CZE, derivative spectrometry and linear voltammetry.

Four analytical methods have been developed for the quality control of pharmaceutical formulations containing the novel antipsychotic drug, olanzapine: high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), derivative spectrometry and linear voltammetry. All methods require only a simple extraction procedure of olanzapine from the tablets before analysis. HPLC with ultraviolet detection at 260 nm is carried out with a C8 column and a mobile phase constituted of acetonitrile and aqueous tetramethylammonium perchlorate. CZE is performed in an uncoated capillary with phosphate buffer, pH 3.0, as the background electrolyte, with UV detection at 214 nm. Spectrophotometry uses the derivative of the spectrum at 298 nm. In linear voltammetric method (LSV) the current intensity of the oxidation wave at +495 mV is measured. All methods gave similar results in terms of precision and accuracy. For HPLC and CZE, repeatability and intermediate precision, expressed by the RSD was better than 1.8%. The accuracy, resulting from recovery experiments, was between 99.9 and 101.1%. Spectrometry and voltammetry gave slightly higher RSD values (up to 2.9%) and a larger variation of the accuracy (the recovery was between 97.8 and 102.6%). However, the requirements for quantitative analysis are fulfilled for all methods.

Antipsychotic Agents↗
PubMed2000

Extractive analysis of aluminum traces in dialysis solutions.

A very sensitive procedure for the fluorimetric determination of aluminum traces in dialysis solutions by means of Mordant Red 19 dyestuff is described with the extraction of the Al complex in isobutylmethylketone. The experimental conditions were studied, in order to obtain the best extraction yield. The emission intensity of the metal chelate, extracted in the organic layer, was measured at 549 nm, exciting at 485 nm. Linearity between emission intensity and Al concentration was found in the 1-30 ng/ml range. The limit of detection was 0.25 ng/ml. The method resulted to be suitable for the determination of Al traces in commercial dialysis solutions for toxicological purposes.

Aluminum↗
PubMed1999

Determination of catecholamines in human plasma by high-performance liquid chromatography with electrochemical detection.

In the present study, assays were improved for the determination of catecholamines in human plasma. High-performance liquid chromatography with electrochemical detection was employed for quantitative analysis. The influence of various parameters on chromatographic performance, such as the composition and the pH of the mobile phase, and the detection potential, was investigated. An accurate solid-phase extraction procedure, after catecholamine complexation with diphenylborate, was developed. The efficiency yield for all catecholamines was in the range 92-98%. Relative standard deviation values for repeatability and for intermediate precision were less than 2% and 3%, respectively, for all three analytes.

Calibration↗
PubMed1999

Enantiomeric separation of fluoxetine and norfluoxetine in plasma and serum samples with high detection sensitivity capillary electrophoresis.

A capillary electrophoresis method was optimized for the stereoselective analysis of the antidepressant drug fluoxetine and its main demethylated metabolite norfluoxetine using a cyclodextrin-modified sodium phosphate buffer at pH 2.5. The combination of a neutral and a negatively charged cyclodextrin, dimethylated-beta- and phosphated-gamma-respectively, provided the baseline enantiomeric separation of the two compounds. The very low concentrations of chiral selectors employed together with the use of a high sensitivity detection cell of special design (zeta-shaped) in a diode array UV detector allowed us to reach a limit of detection of 0.005 and 0.01 microg/mL for fluoxetine and norfluoxetine, respectively. Analysis of fluoxetine and norfluoxetine standard mixtures showed a reproducibility of migration times and peak area and linearity in the concentration range of 0.1-2.0 microg/mL. The optimized method was applied to the analysis of clinical serum and plasma samples of patients under depression therapy. In all the analyzed samples the enantiomeric forms of fluoxetine and norfluoxetine were easily identified. The fluoxetine and metabolite enantiomeric ratio confirmed the stereoselectivity of the metabolic process of the fluoxetine drug in accordance with the literature data.

Antidepressive Agents, Second-Generation↗
PubMed1999

Spectrophotometric determination of silicate traces in hemodialysis solutions.

Reliable methods for the analysis of silicon are of great importance, because it seems that the silicate anion can reduce aluminum bioavailability in patients undergoing dialysis. Thus, a simple and sensitive spectrophotometric method is described for the determination of silicate traces in dialysis solutions. The method is based on the reaction between silicate ions and excess ammonium molybdate reagent to give a yellow silico-molybdic complex. This complex is then reduced to the heteropoly blue compound by means of ascorbic acid. Absorbance values are measured at 830 nm, and are stable for more than 2 h. A good linearity was obtained up to 300 ng ml(-1) of silicon concentration. The accuracy and the precision of the method were good; relative standard deviation values of 2% intraday and of 3.9% interday for six replicates on 40 ng ml(-1) standard silicate solutions were found. Results of the analysis of some commercial hemodialysis solution samples, obtained by means of the 'standard additions' method, are provided.

Aluminum↗
PubMed1999

Experimentally induced aggressiveness in adult children of alcoholics (ACOAs): preliminary behavioral and neuroendocrine findings.

OBJECTIVE: This study was conducted to determine the nature of the reaction of nonalcoholic adult children of alcoholic (ACOA) fathers to the experimental induction of aggression. Of particular interest was the relationship between biochemical factors and personality traits during a stressful event experienced by persons at risk for alcoholism. METHOD: Aggression was induced by a modified free-operant procedure in 14 ACOA and 14 non-ACOA subjects between 18 and 19 years of age with men and women represented in equal numbers. Neurotransmitter-hormonal assays from blood drawn immediately before, and 20 and 30 minutes after, starting the test included norepinephrine (NE), epinephrine (EPI), prolactin (PRL), growth hormone (GH) and cortisol (Cort). Personality traits were assessed by the Minnesota Multiphasic Personality Inventory (MMPI) Tridimensional Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI). RESULTS: During the aggression induction session, ACOAs gained (F = 4.6, 1/13 df, p < .05) and subtracted (F = 9.2, 1/13 df, p < .005) significantly less money than non-ACOAs, evidence of lower outward-directed aggressiveness among ACOAs. Higher baseline plasma levels of Cort (F = 9.8, 1/13 df, p < .01) and PRL (F = 4.0, 1/13 df, p < .05) and decreased NE (F = 8.5, 1/13 df, p < .005) and GH (F = 10.9, 1/13 df, p < .001) responses during the experimental session were observed. On personality measures ACOAs scored higher than non-ACOAs on MMPI hysteria (F = 10.8, 1/13 df, p < .005), hypochondria (F = 20.1, 1/13 df, p < .001) and paranoia (F = 4.7, 1/13 df, p < 0.5) subscales, on the TPQ reward dependence (F = 10.9, 1/13 df, p < .005) subscale and on BDHI guilt (F = 15.7, 1/13 df, p < .001) and resentment (F = 6.4, 1/13 df, p < .05) subscales. CONCLUSION: These findings, preliminary in nature, support a hypothesis of inhibition of state and trait aggression in ACOAs in association with monoaminergic and endocrine changes.

Adolescent↗
PubMed1998

Controlled insulin release from chitosan microparticles.

This study deals with the production of chitosan microparticles containing insulin by interfacial crosslinkage of chitosan solubilized in the aqueous phase of a water/oil dispersion in the presence of ascorbyl palmitate. The use of ascorbyl palmitate as interfacial crosslinker is based on its amphiphilic properties allowing its disposition at the water/oil interface of the preparative dispersion, thus permitting covalent bond formation with the amino groups of chitosan when its oxidation to dehydroascorbyl palmitate takes place during microparticle preparation. This preparation method produced microparticles characterized by high loading levels of insulin, completely releasing the drug in about 80 h at an almost constant release rate as determined by spectrophotometric and spectrofluorimetric methods. In contrast, the replacement of ascorbyl palmitate by dehydroascorbyl palmitate provided microparticles incompletely releasing the incorporated drug and characterized by a non-constant release rate over time due to the higher lipophilicity of dehydroascorbyl palmitate which hinders its disposition at the water/oil interface and thus decreases the crosslinking efficiency and increases the lipophilicity of the microparticle surface. The efficiency of the spectrofluorimetric and spectrophotometric methods used for determination of the stability and release of the insulin from the chitosan microparticles is also discussed.

Ascorbic Acid↗
PubMed1998

Determination of fluoxetine and norfluoxetine in human plasma by high-pressure liquid chromatography with fluorescence detection.

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 microl of plasma, which undergo solid phase extraction (SPE), then are injected in the HPLC. For the analytical separation a reversed phase C8 column (150 x 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 (lambda(exc) = 230 nm, lambda(em)=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(-1) for 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.

Calibration↗
PubMed1998

Analytical methods for the quality control of Prozac capsules.

Some analytical methods (two spectrophotometric and two chromatographic procedures) for the determination of fluoxetine in Prozac capsules are described. All of them are applied to the samples after extracting the drug with a methanol water mixture. The direct and derivative spectrophotometric methods are simple and reliable; the derivative method gives better recovery and lessens interference. Both methods show linearity in the 5-30 microg ml(-1) range of the fluoxetine concentration range. Both HPLC methods (spectrophotometric and spectrofluorimetric detection) use a tetramethylammonium perchlorate buffer-acetonitrile mixture as the mobile phase and a C8 reversed phase column. The UV detection is performed at 226 nm, while the fluorimetric detection is performed by exciting at 230 nm and revealing the emission at 290 nm. The HPLC method with UV detection is more precise, but the procedure with fluorimetric detection is more sensitive.

Antidepressive Agents, Second-Generation↗
PubMed1997

Toxicological assessment of liquorice: biliary excretion in rats.

Glycyrrhizin (G) and its aglycone, glycyrrhetic acid (GA) have been prescribed for several therapeutic purposes. However, side effects have pointed out the problem of the toxicity of G. On the contrary, it was recently shown that the pure aqueous liquorice extract (LE), which also contains G, produces reduced adverse effects in rat and human, as compared to pure G, this is likely be related to differences in G bioavailability and the resulting pharmacokinetics of G and GA. Using a sensitive HPLC procedure for the determination of G and GA in rat bile, pharmacokinetics of G and GA in bile have been determined. The results of the analysis showed significantly lower concentrations of G in bile samples from rats treated with LE compared to pure G. Furthermore, LE presented a significant choleretic effect after both oral and i.v. administration, which increases the excretion rate of G. In case of GA, all the concentrations were very low, often below the detection limit. The results prompted us to assess the risk associated with liquorice intake and to determine the daily amount of pure liquorice root extract that can be safely consumed.

Administration, Oral↗