Hair analysis to discriminate voluntary doping vs inadvertent ingestion of the aromatase inhibitor letrozole.

Letrozole is an aromatase inhibitor, used to treat postmenopausal women with hormone receptor-positive or unknown advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In the case of an adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake.

Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements.

Diuretic agents are prohibited in sports in- and out-of-competition according to the regulations of the World Anti-Doping Agency (WADA) because of their possible masking effects on other doping agents in urine samples, and their ability to produce fast acute weight losses. Despite previous studies reported adverse analytical findings (AAFs) resulting from contaminations at ppm level (μg/g) of medicinal products, and recommended to introduce reporting limits for diuretics in doping controls, these are not adopted in analyses performed by WADA-accredited laboratories. We report the case of an athlete with two AAFs for hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who declared the use of nutritional supplements prepared in a compounding pharmacy.

A Study on Photostability of Amphetamines and Ketamine in Hair Irradiated under Artificial Sunlight.

Drugs incorporated into hair are exposed to the environment, and cosmetic and chemical treatments, with possible decreases in their content. Knowledge concerning the effect of sunlight on drug content in hair can be helpful to forensic toxicologists, in particular, when investigating drug concentrations above or below pre-determined cut-offs. Twenty authentic positive hair samples were selected which had previously tested positive for amphetamines and/or ketamine.

Non-fatal Overdose with U-47700: Identification in Biological Matrices.

Background/objective: We report on a case of severe intoxication after insufflation of U-47700, a synthetic opioid that acts as a selective agonist of the μ-opioid receptor, and is several times more potent than morphine. A man in his 30s was found irresponsive in his apartment and was brought to the emergency department of a local hospital. A comatose state and severe respiratory depression were present.

Photostability of 6-MAM and morphine exposed to controlled UV irradiation in water and methanol solution: HRMS for the characterization of transformation products and comparison with the dry state.

The UVA and UVB light-induced behaviour of 6-monoacetylmorphine (6-MAM) and morphine, the main metabolites of heroin, was studied in methanol, aqueous solution and in the dry state. UVA and UVB irradiations were performed for different times (radiant energies of 20-300J/cm(2)). UV spectra of irradiated samples were compared with samples kept in the dark.

Sample preparation methods for determination of drugs of abuse in hair samples: A review.

Hair analysis has assumed increasing importance in the determination of substances of abuse, both in clinical and forensic toxicology investigations. Hair analysis offers particular advantages over other biological matrices (blood and urine), including a larger window of detection, ease of collection and sample stability. In the present work, an overview of sample preparation techniques for the determination of substances of abuse in hair is provided, specifically regarding the principal steps in hair sample treatment-decontamination, extraction and purification.

GABA Receptors Genes Polymorphisms and Alcohol Dependence: No Evidence of an Association in an Italian Male Population.

Objective: The genes encoding for gamma-aminobutyric acid (GABA) A and B receptors may be considered as candidates for alcoholism; genetic alterations at this level may produce structural and functional diversity and thus play a role in the response to alcohol addiction treatment. To investigate these aspects further, we conducted a preliminary genetic association study on a population of Italian male alcohol addicts, focusing on GABA A and B receptors.

Methods: A total of 186 alcohol-dependent subjects (in the first phase 139, then 47 more samples) and 182 controls were genotyped for 25 single nucleotide polymorphisms (SNPs) of genes encoding the alpha-1 subunit of GABA A receptor (GABRA1) and subunits 1 and 2 of GABA B receptor (GABBR1 and GABBR2).

A study on photodegradation of methadone, EDDP, and other drugs of abuse in hair exposed to controlled UVB radiation.

The drug content of hair may be affected by washing, chemical or thermal treatments, the use of cosmetics, or exposure to the environment. Knowledge concerning the effect of natural or artificial light on drug content in hair can be helpful to the forensic toxicologist, in particular when investigating drug concentrations above or below pre-determined cut-offs. The photodegradation of methadone and its metabolite, 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was studied in authentic positive hair samples by comparing drug concentrations determined by liquid chromatrography-high resolution mass spectrometry before and after exposure to UVB light (in vivo study).

GABA receptors, alcohol dependence and criminal behavior.

The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic-environmental approach. The research, structured as a case-control study, examined 186 alcohol-dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.

Selective intrauterine growth restriction in monochorionic twin pregnancies: markers of endothelial damage and metabolomic profile.

The aim of this study was to assess the aorta-intima thickness (aIT) and serum metabolomic profile in selective intrauterine growth-restricted (sIUGR) monochorionic diamniotic (MCDA) twin fetuses presenting Doppler velocimetry alterations. Fetal abdominal aIT was measured by ultrasound at 32 weeks of gestation, enrolling 24 MCDA twin fetuses (8 sIUGR and 16 controls). sIUGR twin fetuses were classified into two groups: Group 1 consisted of sIUGR with abnormal umbilical artery (UA) Doppler waveforms and Group 2 included sIUGR with normal UA Doppler.

Determination of ketamine and norketamine in hair by micropulverized extraction and liquid chromatography-high resolution mass spectrometry.

Ketamine (KT), primarily used as a general anaesthetic agent in clinical practice, has become very popular in recent years as a recreational drug, due to its dissociative and hallucinogenic effects. A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method has been developed and validated for the quantification of KT and its main metabolite norketamine (NK) in 2.0mg of hair.

Alcohol dependence and criminal behavior: preliminary results of an association study of environmental and genetic factors in an Italian male population.

The aim of this study is to propose an innovative approach evaluating the connection between alcohol use disorders and criminal behavior. The research, structured as a case-control study, was based on the analysis of environmental (social variables) and genetic factors (single nucleotide polymorphisms of glutamic acid decarboxylase) in a population (N = 173) of Italian alcohol-dependent men. Group 1 (N = 47, convicted subjects) was compared with Group 2 (N = 126, no previous criminal conduct).

Changes in amniotic fluid and umbilical cord serum proteomic profiles of foetuses with intrauterine growth retardation.

Foetal growth is a result of a complex net of processes, requiring coordination within the maternal, placental, and foetal compartments, the imbalance or lack of which may lead to intrauterine growth restriction (IUGR). IUGR is the major cause of perinatal morbidity and mortality, and is also related to enhanced morbidity and metabolic abnormalities later in life. In the present study, the protein profiles of umbilical cord serum (UCS) and amniotic fluid (AF) of ten IUGR and ten appropriate for gestational age newborns have been analysed by 2-DE, and nanoHPLC-Chip/MS technology.

Cord blood metabolomic profiling in intrauterine growth restriction.

A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis of cord blood collected soon after birth.

High performance liquid chromatography-high resolution mass spectrometry and micropulverized extraction for the quantification of amphetamines, cocaine, opioids, benzodiazepines, antidepressants and hallucinogens in 2.5 mg hair samples.

A high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) method for simultaneous screening and quantification of 28 drugs was developed and validated for 2.5 mg hair samples. Target drugs and their metabolites included amphetamines, cocaine, opioids, benzodiazepines, antidepressants, and hallucinogens.

Simultaneous LC-HRMS determination of 28 benzodiazepines and metabolites in hair.

A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for the simultaneous identification and quantification of 28 benzodiazepines, including 6 metabolites, in 50 mg of hair has been validated. Positive ion electrospray ionization and HRMS determination in full-scan mode were realized on an Orbitrap mass spectrometer at a nominal resolving power of 60,000. In-source collisional experiments were conducted to obtain additional information for a more reliable identification of the investigated drugs.

Alcohol dependence and glutamate decarboxylase gene polymorphisms in an Italian male population.

Knowledge of alcohol use disorder and of substance-related problems has recently found some initial support in genetic studies. With a view to further understanding of this particular aspect, in the light of the "self-medication hypothesis," we focused our attention on the gamma aminobutyric acid system and, in particular, on single nucleotide polymorphisms (SNPs) in the glutamate decarboxylase 67 or glutamic acid decarboxylase 67 (GAD67) gene region in association with alcohol dependence. The research was structured as a case-control study.