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Biomedical subjects

I Altieri

Publications and source records attributed to I Altieri.

At least 19 recordsLinked to original sources

Determination of lorazepam in plasma and urine as trimethylsilyl derivative using gas chromatography-tandem mass spectrometry.

A procedure based on gas chromatography-tandem mass spectrometry for identification and quantitation of lorazepam in plasma and urine is presented. The analyte was extracted from biological fluids under alkaline conditions using solid-phase extraction with an Extrelut-1 column in the presence of oxazepam-d5 as the internal standard. Both compounds were then converted to their trimethylsilyl derivatives and the reaction products were identified and quantitated by gas chromatography-tandem mass spectrometry using the product ions of the two compounds (m/z 341, 306 and 267 for lorazepam derivative and m/z 346, 309 and 271 for oxazepam-d5 derivative) formed from the parent ions by collision-induced dissociation in the ion trap spectrometer. Limit of quantitation was 0.1 ng/ml. This method was validated for urine and plasma samples of individuals in treatment with the drug.

Anti-Anxiety Agents↗

Determination of opiates and cocaine in hair as trimethylsilyl derivatives using gas chromatography-tandem mass spectrometry.

An analytical method for the determination of heroin, 6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine, and cocaethylene in human hair using gas chromatography-tandem mass spectrometry is presented. The analytes were extracted from finely cut hair with methanol at 56 degrees C for 18 h in the presence of nalorphine as the internal standard. After the incubation, methanol was evaporated to dryness, and all the analytes, except heroin, cocaine, and cocaethylene, were converted to their trimethylsilyl derivatives. The reaction products were identified and quantitated using product ions formed from the parent ions by collision-induced dissociation in the ion-trap mass spectrometer. This method provided excellent sensitivity and specificity for analytes at the concentrations usually found in the keratin matrix.

Cocaine↗

Simultaneous determination of epirubicin, doxorubicin and their principal metabolites in human plasma by high-performance liquid chromatography and electrochemical detection.

A high-performance liquid chromatographic method with electrochemical detection has been developed for the simultaneous determination of epirubicin, 13-S-dihydroepirubicin, doxorubicin and 13-S-dihydrodoxorubicin in human plasma. An aliquot of 200 microl plasma, spiked with internal standard, was extracted by solid-phase extraction using polymeric adsorbent columns. Chromatography was performed using a C18 reversed-phase column with a mobile phase consisting of water-acetonitrile (71:29, v/v) containing 0.05 M Na2HPO4 and 0.05% v/v triethylamine adjusted to pH 4.6 with citric acid. Linearity of the method was obtained in the concentration range of 1-500 ng/ml for all the analytes. Analytical recoveries of the analytes ranged from 89 to 93%. The assay can be used for the simultaneous determination of the four analytes, or for epirubicin and its metabolite or doxorubicin and its metabolite, using the other parent drug as an internal standard. The method was applied to analyze human plasma samples from patients treated with epirubicin using doxorubicin as an internal standard.

Antibiotics, Antineoplastic↗

Issues in methodology and applications for therapeutic drug monitoring of fluoxetine and norfluoxetine enantiomers.

A standardization of the analytical procedures for monitoring of fluoxetine and norfluoxetine enantiomers is described. Simultaneous determination of fluoxetine and norfluoxetine enantiomers in plasma and serum was performed by high-performance liquid chromatography with a chiral stationary phase, using ultraviolet absorbance detection. The analytes were extracted from the biologic matrix by alkalinization with NaOH and solid-phase extraction. Stability studies were conducted in EDTA, lithium-heparinized plasma and in serum spiked with the analytes stored at +4 degrees C for 1 week and at -20 degrees C for 1 month. Furthermore, stability studies in NaOH and in the extraction solvents were executed. Using this methodology, EDTA plasma is the most suitable matrix for drug monitoring, even if the storage should not exceed 3 weeks at -20 degrees C. Furthermore, the biologic sample should be left in NaOH for a short time before solid-phase extraction to prevent a degradation of matrix, which would interfere with the chromatographic analysis.

Chromatography, High Pressure Liquid↗

Hair analysis for nicotine and cotinine: evaluation of extraction procedures, hair treatments, and development of reference material.

Analysis of nicotine and cotinine in human hair can provide information on nicotine intake and exposure to environmental tobacco smoke over a long period of time. Nonetheless, to better assess the usefulness of hair analysis to determine smoking habits or exposures, all procedures have to be standardized. Various solvents were tested as washing solvents to eliminate external contamination from nicotine. Dichloromethane was found effective when used for two washes prior to the extraction. Basic and acid digestion of hair followed by solid phase extraction with Extrelut-3 glass column using dichloromethane:isopropyl alcohol (9:1) as eluting mixture both gave good recoveries of nicotine and cotinine, when compared with extractions reported in the literature. The extraction method was free from substances, which could interfere in the chromatographic analysis. Furthermore, the addition of methanolic HCl to the eluting mixture prevented the loss of nicotine during the evaporation step before chromatography. Chromatography was performed using a reversed-phase column and a U.V. detection at 254 nm. Furthermore, hair treatments (dyes, permanent wave, hydrogen peroxide) caused a major decrease in the nicotine content in hair, and a smaller effect on cotinine levels. However, the effect of various treatments was not reproducible. Several attempts to produce reference materials were carried out. Nicotine and cotinine standard solutions at different concentrations were added to blank hair soaked in dimethylsulfoxide, methanol and water.

Chromatography, High Pressure Liquid↗

The analysis of nicotine in infants' hair for measuring exposure to environmental tobacco smoke.

Hair samples were collected from 24 infants (3-36 months) exposed and non-exposed to environmental tobacco smoke. Hair was washed in dichloromethane, digested in NaOH, extracted by solid-phase extraction and analyzed by high-performance liquid chromatography to determine the content of nicotine and cotinine. Nicotine concentration in non-exposed infants (1.3 +/- 1.7 ng/mg hair) was significantly different from that in occasionally exposed infants (6.8 +/- 2.1 ng/mg hair) and that in infants passively exposed to smoke (15.4 +/- 6.7 ng/mg hair). Cotinine could be measured only in passive smokers infants. These findings suggest the possibility of monitoring exposure to environmental tobacco smoke in infants by using nicotine measurement in hair rather than in urine, blood or saliva.

Biomarkers↗

Drug monitoring in nonconventional biological fluids and matrices.

Determination of the concentration of drugs and metabolites in biological fluids or matrices other than blood or urine (most commonly used in laboratory testing) may be of interest in certain areas of drug concentration monitoring. Saliva is the only fluid which can be used successfully as a substitute for blood in therapeutic drug monitoring, while an individual's past history of medication, compliance and drug abuse, can be obtained from drug analysis of the hair or nails. Drug concentrations in the bile and faeces can account for excretion of drugs and metabolites other than by the renal route. Furthermore, it is important that certain matrices (tears, nails, cerebrospinal fluid, bronchial secretions, peritoneal fluid and interstitial fluid) are analysed, as these may reveal the presence of a drug at the site of action; others (fetal blood, amniotic fluid and breast milk) are useful for determining fetal and perinatal exposure to drugs. Finally, drug monitoring in fluids such as cervical mucus and seminal fluid can be associated with morpho-physiological modifications and genotoxic effects. Drug concentration measurement in nonconventional matrices and fluids, although sometimes expensive and difficult to carry out, should therefore be considered for inclusion in studies of the pharmacokinetics and pharmacodynamics of new drugs.

Biological Availability↗

Household and community determinants of exposure to involuntary smoking: a study of urinary cotinine in children and adolescents.

The study examines the role of several potential predictors of urinary cotinine levels in a cross-sectional sample of 1,072 nonsmoking children and adolescents in Latium, Italy, during 1990-1991. As expected, there was a strong relation between passive exposure to smoking and the amount of maternal and paternal self-reported smoking. The urinary cotinine level increased with a decreasing level of paternal education and with an increasing index of household crowding; self-report of recent exposure to smoking outside the home was a strong predictor of the biologic marker. The analysis was then restricted to 346 subjects whose parents claimed that they were nonsmokers and that there were no smokers at home. In this group, however, 57 children reported some active smoking at home by their parents. Those with parents suspected to be "deceivers" had higher level of urinary cotinine than did those truly not exposed. In addition, urinary cotinine in this group was clearly associated with duration of exposure to smoking outside home. The study indicates that both factors related to family circumstances and exposure outside the household setting are strong determinants of urinary cotinine levels. The finding may be considered a direct confirmation that passive smoking among children should be viewed as a specific community responsibility.

Adolescent↗

Improved clean-up procedure for the high-performance liquid chromatographic assay of clomipramine and its demethylated metabolite in human plasma.

A rapid and selective assay of clomipramine and its metabolite desmethylclomipramine in human plasma, based on high-performance liquid chromatography with UV detection has been developed. The compounds were subjected to solid-phase extraction, using Extrelut 1 cartridges. Recoveries ranged between 88-95% for clomipramine, and 75-80% for desmethylclomipramine. This method has been used for therapeutic monitoring of clomipramine and its metabolite in individuals treated with this drug.

Antidepressive Agents, Tricyclic↗

Solid-phase extraction of nicotine and its metabolites for high-performance liquid chromatographic determination in urine.

A solid-phase extraction, using Extrelut-1 glass columns, has been applied to urine samples of both passive and active smokers for high-performance liquid chromatographic determination of nicotine and its metabolites cotinine and trans-3'-hydroxycotinine. Chromatography was performed using a reversed-phase LC8DB column and a mobile phase consisting of water-acetonitrile (80:9, v/v) containing 5 ml triethylamine, 670 mg/l sodium heptanesulphonate, and 0.034 M each of K2HPO4 and citric acid (pH 4.4), at a flow-rate of 1.6 ml/min. The results obtained indicate that solid-phase extraction is a reliable and quick procedure which can be applied also to other nicotine metabolites.

Chromatography, High Pressure Liquid↗

High-performance liquid chromatographic-electrospray mass spectrometric determination of morphine and its 3- and 6-glucuronides: application to pharmacokinetic studies.

A rapid and selective assay of morphine and its 3- and 6-glucuronides in serum, based on high-performance liquid chromatography-electrospray mass spectrometry has been developed. The analytes and the internal standard, codeine or naltrexone, were subjected to solid-phase extraction, using ethyl solid-phase extraction columns, prior to chromatography. A reversed-phase column and a gradient mobile phase consisting of water and methanol were used. The mass spectrometer was operated in the selected-ion monitoring mode. The following ions were used: m/z 286 for morphine, m/z 300 for codeine, m/z 342 for naltrexone, and m/z 462 for morphine 3- and 6-glucuronides. The limit of quantitation observed with this method was 10 ng/ml morphine, 50 ng/ml morphine-6-glucuronide and 100 ng/ml morphine-3-glucuronide. The present method proved useful for the determination of serum levels of the parent drug and its metabolites in pain patients, heroin addicts and in morphine-treated mice.

Animals↗

Environmental tobacco smoke: nicotine and cotinine concentration in semen.

Forty-three nonsmokers attending an infertility clinic reported their degree of passive exposure to environmental tobacco smoke (ETS) and provided samples of blood and seminal plasma. Levels of nicotine and cotinine in biological fluid were evaluated by a radioimmunoassay. The data indicate that exposure to ETS results in measurable nicotine and cotinine levels in seminal plasma. Seminal plasma cotinine concentration also shows a significant positive correlation with degree of reported exposure.

Adult↗

Personality, endocrine and immune changes after eight months in healthy individuals under normal daily stress.

The impact of stress and its neuroendocrine correlates on immune function are well established and individual variations could be attributed to modulation by personality characteristics. To assess the influence of everyday life stress and personality on neuroendocrine and immune function, we administered, to 18 healthy adults, the Minnesota Multiphasic Personality Inventory (MMPI) to assess their personality, the State-Trait Anxiety Inventory to measure anxiety, the Reaction Scheme Test to assess their coping reaction style, the Life Events Survey to assess the impact of stressful life events, and the Subjective Stress Questionnaire to assess perceived stress. The endocrine evaluation comprised prolactin, cortisol, and growth hormone plasma levels, while the immunological evaluation assessed T4, T8, and T11 lymphocyte percentages, as well as natural killer cell count and activity. All evaluations were made at baseline and after 8 months. We found a reduction of the T11 lymphocyte percentage to be accompanied by a reduction in the scores of the MMPI scale of Subtle Defensiveness and by an increase in the scores of the Social Introversion Scale. A positive correlation was found between prolactin and T4 lymphocyte percentage. These preliminary data show that some personality and endocrine measures correlate with immune function.

Adult↗

Determination of nicotine and four metabolites in the serum of smokers by high-performance liquid chromatography with ultraviolet detection.

A simple and reliable reversed-phase high-performance liquid chromatographic method with ultraviolet detection is described for the quantitation of nicotine and its metabolites cotinine, trans-3'-hydroxycotinine, norcotinine and cotinine N-oxide in human serum. The analytes and the internal standard, N-ethylnorcotinine, were extracted by solid-phase extraction before chromatography. Two different columns and mobile phases with gradient systems were used. The detection limit of the assay was 10 ng/ml for nicotine, 3 ng/ml for cotinine N-oxide and 5 ng/ml for cotinine, trans-3'-hydroxycotinine and norcotinine. The concentrations of nicotine and its metabolites in the serum of 12 cigarette smokers are reported.

Chromatography, High Pressure Liquid↗

Modified procedure for labelling target cells in a europium release assay of natural killer cell activity.

Lanthanide europium chelated to diethylenetriaminopentaacetate (EuDTPA) can be used to label target cells such as tumor cells and lymphocytes (Blomberg et al., 1986a,b; Granberg et al., 1988). This procedure has permitted the development of new non-radioactive methods for the detection of target cell cytolysis by natural killer (NK) cells (Blomberg et al., 1986a,b), cytotoxic T lymphocytes (CTL) (Granberg et al., 1988) or complement-mediated cytolysis (Cui et al., 1992). However, we had no success with this method because of a lack of comparability between human NK cell activity simultaneously measured by a classical 51Cr release assay (Seaman et al., 1981) and EuDTPA release assay (Blomberg et al., 1986a). Furthermore, cell division and cell viability were significantly impaired by the suggested concentrations of EuCl3. In this paper, we present a modified non-cytotoxic method for target cell labelling with EuDTPA while cells are growing in culture medium.

Cytotoxicity Tests, Immunologic↗

Determination of nicotine and two major metabolites in serum by solid-phase extraction and high-performance liquid chromatography, and high-performance liquid chromatography-particle beam mass spectrometry.

A rapid and selective assay of nicotine, cotinine and trans-3'-hydroxycotinine in human serum, based on high-performance liquid chromatography with UV detection has been developed. The compounds were subjected to solid-phase extraction, using Extrelut 1 cartridges. Recoveries were ca. 95% for nicotine, 90% for cotinine and 50-55% for trans-3'-hydroxycotinine. The limit of quantitation observed with this method was 10 ng/ml for nicotine and 5 ng/ml for each of the metabolites. The compounds were also identified using high-performance liquid chromatography with particle beam mass spectrometry, to confirm their presence in human serum.

Chromatography, High Pressure Liquid↗