Teodora Macchia

Simultaneous detection of amphetamine-like drugs with headspace solid-phase microextraction and gas chromatography-mass spectrometry.

A headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME-GC-MS) procedure for the simultaneous detection of methylen-dioxyamphetamine (MDA), methylen-dioxymethamphetamine (MDMA), methylen-dioxyethamphetamine (MDE) and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) in hair has been developed. This method is suitable for the separation of primary and secondary amines, is reproducible, is not time consuming, requires small quantities of sample and does not require any derivatization. It provides sufficient sensitivity and specificity, with limits of detection (LOD) and limits of quantitation (LOQ) for each substance of <0.7 and 1.90 ng/mg, respectively. Intra- and inter-day precision were within 2 and 10%, respectively. This method is suitable for routine clinical, epidemiological and forensic purposes and can be used for the preliminary screening of many other substances (amphetamine, methamphetamine, ketamine, ephedrine, nicotine, phencyclidine, methadone) in hair and other biological matrices such as saliva, urine and blood. We also describe the first application of this HS-SPME-GC-MS procedure to the analysis of hair and saliva samples from young people attending a disco in the Rome area. All positive hair samples were confirmed by the gas chromatography-mass-mass (GC-MS(2)) technique in positive chemical ionization (PCI) mode. Some examples of the use of the method in detecting different drugs are reported.

Chiral separation of 12 cathinone analogs by cyclodextrin-assisted capillary electrophoresis with UV and mass spectrometry detection

In this study, a rapid chiral separation of 12 cathinones analogs has been developed and validated using cyclodextrin‐assisted CE with UV and TOF‐MS detection. Optimum separation was obtained on a 57.5 cm × 50 μm capillary using a buffer system consisting of 10 mM β‐cyclodextrin (β‐CD) in a 100 mM phosphate buffer for CE‐UV, and 0.6% v/v highly sulfated‐γ‐cyclodextrin (HS‐γ‐CD) in a 50 mM phosphate buffer for CE‐MS. In the CE‐MS experiment, a partial filling technique was employed to ensure that a minimum amount of cyclodextrin entered the mass spectrometer. All analytes were separated within 18 min in the CE‐UV separation and identified by TOF‐MS. Ten compounds were enantiomerically separated using β‐CD in the UV mode and an additional two more were enantiomerically separated using HS‐γ‐CD in the MS mode. Detection limits down to 1.0 ng/mL were obtained. The method was then applied to examine seized drugs.

Analysis of synthetic cannabinoids in herbal blends by means of nano-liquid chromatography

In this study, a rapid and simultaneous separation of 12 synthetic cannabinoids and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) in herbal blends was obtained by means of nano-liquid chromatography (nano-LC). The nano-LC experiments were performed in a 100μm i.d. capillary column packed with Cogent(®) bidentate C(18) silica particles for 25.0cm. All compounds were resolved using an isocratic elution mode in less than 30min. A mobile phase containing ACN/MeOH/H(2)O/formic acid 69/5/25/1 (v/v/v/v) was employed for the chromatographic separation. The developed analytical method was validated in terms of precision, linearity, sensitivity and accuracy. Under optimal nano-LC-UV conditions, the resulting RSD percentages for intra-day and inter-day repeatability, related to retention time and peak area, were below 2.98 and 6.40%, respectively. Limits of detection and quantification were 0.2 and 0.5μg/mL, respectively, for all the studied compounds. Linearity was assessed in the concentration range of interest for all analytes with determination coefficients r(2)≥0.9975. The method was then applied to the determination of synthetic cannabinoids in herbal blends. Quantitative analyses of the cannabimimetic compounds in six products showed that there was a wide difference in the concentration of the studied compounds among different products. Further, the nano-LC system was coupled with a mass spectrometer measuring the MS and MS-MS spectra to unequivocally identify the cannabinoids present in smoking mixtures.

Effects of (±) 3,4-methylene–dioxymethamphetamine (ecstasy) on dopamine system function in humans

Twelve (+/-) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse (group A), and 12 control subjects (group B) were included in the study. Prolactin (PRL) and growth hormone (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in A and B subjects after BROM suppression, without any significant difference between the two groups. PRL responses to BROM in MDMA users were in the normal range. In contrast, GH responses to BROM stimulation were found significantly reduced in ecstasy users, in comparison with control subjects (P < 0.001; F = 6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs) showed a significant inverse correlation with NS scores both in A and B subjects. GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA users. No other psychometric measure correlated with hormonal responses. GH AUCs were inversely correlated with the measures of MDMA exposure (r = -0.48; P < 0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced D2 receptor sensitivity in the hypothalamus, possibly due to increased intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic changes associated with a premorbid condition cannot be completely excluded, the inverse correlation between DA receptors sensitivity and the extent of ecstasy exposure may suggest a direct pharmacological action of MDMA on brain dopamine function in humans.

Prevalence of Sexual Disorders in Those Young Males Who Later Become Drug Abusers

The purpose of this study was to learn about the frequency of sexual disorders in young males who later become substance abusers. We interviewed 228 men treated in 10 drug centers for substance abuse. The questionnaire that we used was designed to assess the onset of erectile dysfunction (ED) or of premature ejaculation (PE). Only those subjects who became substance users between the ages of 17 to 29 were taken into consideration. Of the 228 subjects recruited, only 130 met the inclusion criteria (mean age 33). These male patients had a prevalence of ED of 20.3% (cl 99% 12.3-31.2), whereas the prevalence of ED of age-matched males in the general population is 2.1% (cl 99% 0.36-5.46; p

Neuroendocrine correlates of depression in abstinent heroin-dependent subjects

The functions of the central alpha-adrenergic, serotoninergic and dopaminergic systems were investigated in 28 heroin-dependent subjects 6-8 weeks after detoxification, and in 22 healthy control subjects (group C). Fourteen heroin-dependent subjects with depressive comorbidity (group A), and 14 heroin-dependent subjects without other Axis I and II pathologies (group B) were included among abstinent substance abusers. Norepinephrine (NE) function was evaluated by growth hormone (GH) responses to acute stimulation with clonidine (clon); serotonin (5-HT) function by prolactin (PRL) and cortisol (CORT) responses to acute stimulation with D-fenfluramine (D-fen) and dopamine (DA) function by GH and PRL responses to acute administration of bromocriptine (brom). Central NE activity, as measured by the GH-clon test, seems to be well preserved both in A and B subjects. PRL and CORT responses to D-fen were significantly blunted both in A subjects and in B subjects, in comparison with control subjects (C); the PRL response in A subjects was significantly lower than in B subjects. The DA system of B subjects was found unimpaired; in contrast, a significantly higher GH response to brom in A subjects (depressed) could express D2 post-synaptic receptor hypersensitivity and, therefore, decreased pre-synaptic DA release. In sum, the study of central monoamine function revealed an alteration only of the 5-HT system in detoxified heroin-dependent subjects without psychiatric comorbidity, which might be a trait character of these subjects, possibly involved in the pathogenesis of the disorder. A more significant impairment of 5-HT function and the hypersensitivity of post-synaptic DA receptors in A subjects suggests that specific biological correlates of psychiatric comorbidity may characterize substance abuser subtypes.

Simple and reliable high-performance liquid chromatography fluorimetric procedure for the determination of amphetamine-derived designer drugs.

The paper describes a HPLC-fluorimetric procedure for the determination of methylenedioxyamphetamine, methylenedioxymethamphetamine, methylenedioxyethamphetamine and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine in urine, serum, saliva and street samples, that features interesting advantages over other procedures previously described. The method requires a very small sample volume (100 microl) and no extraction, lacks matrix effect, and is not time consuming. Linearity was in the range 50-1000 ng/ml regardless of matrix. Sensitivity and detection limit were 50 ng/ml and 10 ng/ml, respectively, but they may reach 10 ng/ml and 2 ng/ml if a slight modification is introduced in the procedure. Intra- and inter-day precision were always within 5% and 8%, respectively. Recovery was satisfactory for all matrices. The described procedure could be successfully used for clinical, epidemiological and forensic applications.

Mitochondrial aspartate aminotransferase isoenzyme: A biochemical marker for the clinical management of alcoholics?

Serum mitochondrial and total aspartate aminotransferase activity was quantified by a characterized immunochemical method in 126 subjects, 44 healthy controls and 82 chronic alcoholics (51 outpatients and 31 monitored through 15 days). The monitored alcoholics were divided into actual abstinents (n = 21) and drinkers (n = 10) by blood ethanol concentration performed daily. The aims of the present study were: (a) to compare the diagnostic diagnostic usefulness of the mitochondrial isoenzyme and the mitochondrial/total aspartate aminotransferase ratio to detect problematic drinkers; (b) to evaluate the suitability of these indices to monitor abstinence, a difficulty not yet solved in the clinical management of alcoholics. The results demonstrated the mitochondrial isoenzyme to be more suitable to discriminate between controls and alcoholics (Kruskal and Wallis ANOVA, Bonferroni test, P < 10(-5) and mostly between actual drinkers and other alcoholics (P < 0.041). So acute alcohol consumption may be a significant, suggestive and until now inadequately examined factor in evaluating the suitability of mAST as a marker. The results, showing that mAST peaks quickly appear in the presence of a new alcohol intake, should indicate mAST as a possible marker of acute alcohol intake useful in checking self-claimed abstinence.

T09-P-08 Can sexual dysfunctions lead to substance abuse disorders?

Aim To evaluate the role of sexual dysfunctions in inducing the use of drug in young males Methods 185 former heroin addicts from 14 drug rehabilitation centres were invited to fill in a questionnaire with their personal data, toxicological history, sexual experiences as well as quality of performances. Results 60 subjects (32% ) of the sample claimed that their sexual disorder had influenced their decision to start taking drugs. Prior to first drug use the more severe the sexual dysfunction, the higher the percentage of those who stated that sexual dysfunction influenced their decision to start taking drugs. Among those with premature ejaculation and erectile dysfunction this percentage rose to 58.6%. 39% of subject with E.D. used heroin to improve rigidity while among those with premature ejaculation 55% used heroin to improve ejaculation control. Conclusions • Sexual dysfunctions is a risk factor for addiction and can lead to first drug use • The more severe the sexual dysfunction the higher the risk • Heroin and other drugs are used to improve sexual performances and particularly to improve ejaculation control • These data highlight the possibility of primary prevention of substance abuse and addiction with sexual education and early treatment of sexual dysfunctions.