Development and validation of a liquid chromatography-tandem mass spectrometry assay for hair analysis of atomoxetine and its metabolites: Application in clinical practice

Atomoxetine (ATX) is a potent inhibitor of the noradrenaline reuptake transporter approved since 2002 for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults as alternative treatment to methylphenidate. A procedure based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of ATX and its main metabolites (4-hydroxyatomoxetine - 4 hydroxyATX - and N-desmethylatomoxetine - des-methylATX) in hair of one treated child and five treated adolescents. Since hair samples can be easily collected without the need for specials skills and exposing a patient to discomfort, hair testing of ATX and eventually of its metabolites should be useful, especially in case of pediatric patients, to check compliance in a wider time-window. After addition of duloxetine as internal standard, hair samples were overnight digested with 2ml 1M NaOH at 45°C. Then, analytes were extracted from alkaline solution with two different 2ml aliquots of tert-butyl methyl ether. Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a mobile phase of 40% of water-60% 5mM ammonium acetate, 50mM formic acid, 4mM trifluoroacetic acid in acetonitrile-water (85:15, v/v). The mass spectrometer was operated in positive ion mode using multiple reaction monitoring. The method was linear over the concentration range 0.2-50ng/mg hair for the all analytes under investigation, with an intra- and inter-assay imprecision and inaccuracy always less than 20% and an analytical recovery between 33.1% and 76.1%, depending on the considered analyte. Only ATX and 4-hydroxyATX were detected in hair samples with concentrations varying from 0.2 to 2.0ng/mg hair and from 0.3 to 1.0ng/mg, respectively. Notwithstanding the absence of any dose-hair concentration relationship, hair monitoring of ATX and concomitant medications commonly administrated in ADHD children and adolescents can be crucial in verifying long-term compliance to prescribed medication in individuals displaying a non negligible tendency to refuse drugs and to lie on the adherence to therapy as a specific symptom of the disease.     

Acute flurazepam intoxication: a case report

A fatality due to ingestion of flurazepam is reported. Flurazepam is a benzodiazepine, a widely prescribed hypnotic drug for use in sleep disorders. There are only few documented reports of the disposition of flurazepam in deaths due to overdose. A 68-year-old woman was found deceased at home with no evidence of trauma or asphyxia. Toxicologic analyses were performed and drug levels measured by means of gas chromatography coupled to mass spectrometry. The flurazepam concentration in each specimen was as follows: heart blood 2.8 microg/mL, bile 323 microg/mL, and urine 172 microg/mL. Presence of flurazepam into gastric content was observed too. Based on the autopsy findings, patient history, and toxicologic results, the cause of death was determined to be acute intoxication of flurazepam and the manner, suicide.     

Genetic data on nine STRs (CSF1PO, TPOX, THO1, F13AO1, FESFPS, vWA, D16S539, D7S820 and D13S317) and two VNTRs (D1S80 and D17S5) in Rosario population, Santa Fe Argentine

Allele frequencies for nine short tandem repeats (STRs) loci (CSF1PO, TPOX, THO1, F13AO1, FES/FPS, vWA, D16S539, D7S820 and D13S317) and two variable number tandem repeats (VNTRs) were obtained from a sample of 270 unrelated individuals born in the Rosario city, Santa Fe province of Argentina.     

The Impact of Environmental Factors on the Measurement of Managerial Efficiency in the Italian Waste Management Sector: Framework and Empirical Evidence

ABSTRACT

The public and private sectors are different in terms of ownership, funding, and control. The degree of publicness influences the decision-making processes, strategies, and actions, thus severely impacting the performance levels. This study contributes to the existing literature on managerial efficiency environmental factors by proposing a framework and methodology for estimating the influence of the “publicness effect.” A new method is tested, relying on the combined integration of three different data envelopment analysis models in the Italian waste management sector. Results show that the “publicness effect” accounts for 33.87% of managerial efficiency for public companies and 11.6% for mixed ones.     

Problems of corruption and distrust in political and administrative institutions in Slovenia

Corruption is perceived in all societies as a social pathology that causes great material and moral damage and is a threat to the society's continual development. Especially in countries with a freshly consolidated democracy, as Slovenia, the phenomena of corruption must be treated with all due attention. This article emphasises that corruption in Slovenia is publicly perceived as one of the most important and even increasing problems in society. We are also analysing one of the crucial side effects of the corruption, resulting itself in ever deeper public distrust to most significant political and administrative institutions.     

A Very Unusual Accidental Mechanical Asphyxia of Choking with a Whole Solea Solea

The case here reported involves a schizophrenic 19‐year‐old girl under treatment with clotiapine, which was well tolerated except for a moderate dry mouth. The woman ingested a whole sole (Solea solea), which caused a very rapid death by choking. A complete autopsy was performed 24 h later, as well as histological and toxicological analysis. At autopsy, the sole was wedged in the esophagus causing a choking ab extrinseco. The fish had a length of 18 cm and a maximum width of 6 cm, weighing 188.7 g. Toxicological analysis detected 0.57 mg/L of clotiapine in blood, which falls within the therapeutic range. The peculiarity of this case is represented by two factors: one is the choking by fish and the second was the adverse affect caused by clotiapine, which induced a condition of dry mouth making the act of swallowing even more difficult, thereby contributing to a very rapid mechanical asphyxia and the death of the young woman.     

Self‐harm Risk Among Adolescents and the Phenomenon of the “Blue Whale Challenge”: Case Series and Review of the Literature

The “Blue Whale Challenge” is a dangerous Internet phenomenon. As per media reports, it involves a series of life‐threatening tasks imposed by a “curator” to “players,” who must fulfill the whole list, and it ends with the suicide of the player. The authors report the data of five suspected cases of “Blue Whales” managed from January 2016 to December 2017 by the staff of a unit (the “Bambi Unit” of the Pediatric Hospital “Regina Margherita” of Turin, Italy) that is dedicated to the evaluation of suspected abused children. Then, they analyzed this data in the light of the literature regarding self‐harm. This comparison highlights the role of the Internet in the spreading of self‐harm behavior among vulnerable adolescents who are characterized by epidemiological, psychological, psychiatric, social, and cultural risk factors. In conclusion, the authors suggest a multidisciplinary and specialized approach in the evaluation of adolescents who committed self‐harm activities.     

Recuperative memory in Romanian post-Communist society

This paper explores the idea of “recuperative memory” with respect to the process of coming to terms with the past after the fall of the Romanian Communist regime in 1989. Its method is to examine the mechanisms used by recuperative memory in order to re-appropriate the past and emphasize the inherently mediated and multifaceted nature of this process. Using various examples from oral testimonies, autobiographical writings, literary works, and cinema, the paper argues that the role of recuperative memory is not only to facilitate the process of coming to terms with the past, but also to offer the material necessary to sustain a viable politics of memory. This entails providing a platform for the intergenerational transmission of memory and knowledge for those who did not live under the Communist regime, filling in this way the intergenerational gap, despite the lack of political class engagement.