Development and validation of a GC-MS method for the detection and quantification of clotiapine in blood and urine specimens and application to a postmortem case

INTRODUCTION: Clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few European countries since 1970, efficient in treatment-resistant schizophrenic patients. There is little published data on the therapeutic and toxic concentrations of this drug. AIMS: The aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS). METHODS: Validation was performed working on spiked postmortem blood and urine samples. Samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. Methadone-d9 was used as internal standard. RESULTS: The limit of detection (LOD) was 1.2 and 1.3 ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3 ng/mL, respectively. Linearity, precision, selectivity, accuracy, and recovery were also determined. The method was applied to a postmortem case. The blood and urine clotiapine concentrations were 1.32 and 0.49 μg/mL, respectively. CONCLUSIONS: A reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case

Development and Validation of a GC-MS Method for the Detection and Quantification of Clotiapine in Blood and Urine Specimens and Application to a Postmortem Case

clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few european countries since 1970, efficient in treatment-resistant schizophrenic patients. there is little published data on the therapeutic and toxic concentrations of this drug. aims. the aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS).Methods. validation was performed working on spiked postmortem blood and urine samples. samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. methadone-d9 was used as internal standard. results. the limit of detection (LOD) was 1.2 and 1.3 ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3 ng/mL, respectively. linearity, precision, selectivity, accuracy, and recovery were also determined. the method was applied to a postmortem case. the blood and urine clotiapine concentrations were 1.32 and 0.49 μg/mL, respectively.conclusions. a reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case

Sensory contribution to vocal emotion deficit in patients with cerebellar stroke

In recent years, there has been increasing evidence of cerebellar involvement in emotion processing. Difficulties in the recognition of emotion from voices (i.e., emotional prosody) have been observed following cerebellar stroke. However, the interplay between sensory and higher-order cognitive dysfunction in these deficits, as well as possible hemispheric specialization for emotional prosody processing, has yet to be elucidated. We investigated the emotional prosody recognition performances of patients with right versus left cerebellar lesions, as well as of matched controls, entering the acoustic features of the stimuli in our statistical model. We also explored the cerebellar lesion-behavior relationship, using voxel-based lesion-symptom mapping. Results revealed impairment of vocal emotion recognition in both patient subgroups, particularly for neutral or negative prosody, with a higher number of misattributions in patients with right-hemispheric stroke. Voxel-based lesion-symptom mapping showed that some emotional misattributions correlated with lesions in the right Lobules VIIb and VIII and right Crus I and II. Furthermore, a significant proportion of the variance in this misattribution was explained by acoustic features such as pitch, loudness, and spectral aspects. These results point to bilateral posterior cerebellar involvement in both the sensory and cognitive processing of emotions

Seeing your error alters my pointing: observing systematic pointing errors induces sensori-motor after-effects

During the procedure of prism adaptation, subjects execute pointing movements to visual targets under a lateral optical displacement: as consequence of the discrepancy between visual and proprioceptive inputs, their visuo-motor activity is characterized by pointing errors. The perception of such final errors triggers error-correction processes that eventually result into sensori-motor compensation, opposite to the prismatic displacement (i.e., after-effects). Here we tested whether the mere observation of erroneous pointing movements, similar to those executed during prism adaptation, is sufficient to produce adaptation-like after-effects. Neurotypical participants observed, from a first-person perspective, the examiner's arm making incorrect pointing movements that systematically overshot visual targets location to the right, thus simulating a rightward optical deviation. Three classical after-effect measures (proprioceptive, visual and visual-proprioceptive shift) were recorded before and after first-person's perspective observation of pointing errors. Results showed that mere visual exposure to an arm that systematically points on the right-side of a target (i.e., without error correction) produces a leftward after-effect, which mostly affects the observer's proprioceptive estimation of her body midline. In addition, being exposed to such a constant visual error induced in the observer the illusion "to feel" the seen movement. These findings indicate that it is possible to elicit sensori-motor after-effects by mere observation of movement errors

New Psychoactive Substances: Evolution in the Exchange of Information and Innovative Legal Responses in the European Union

Abstract: At the end of 2019, the European Monitoring Centre for Drugs and Drug Addiction was monitoring around 790 new psychoactive substances, more than twice the total number of controlled substances under the United Nations Conventions. These substances, which are not subject to international drug controls, include a wide range of molecules, including the assortment of drugs such as synthetic cannabinoids, stimulants, opiates, and benzodiazepines. Most of them are sold as “legal” substitutes for illicit drugs, while others are intended for small groups willing to experiment with them in order to know their possible new effects. At the national level, various measures have been taken to control new substances and many European countries have responded with specific legislationinfavorofconsumersafetyandbyextendingoradaptingexistingdruglawstoincorporate the new psychoactive substances. Moreover, since 1997, an early warning system has been created in Europe for identifying and responding quickly to the risks of new psychoactive substances. In order toestablishaquickerandmoreeffectivesystemtoaddressthecriminalactivitiesassociatedwithnew dangerous psychoactive substances, the European legal framework has considerably changed over the years

Human biomonitoring in the area around the petrochemical site in Gela, Sicily-Italy

Close to the town of Gela (Sicily, Italy) a petrochemical site is operating since 1962. A power station, chemical plants and an oil refiney plant incleded. In 1990 a large area around the site was declared " at high risk of environmental cirsis" in 2000 a subarea was designated " Reclamation Site of National Inerest" Extremely high concentrations of hazardous chemicals have been measured in soil, surface and groundwater, in marine water and sediments. Mortality, hospital discharges and birth defects were reported higher than neighbouring areas and other references

Unilateral Spatial Neglect

Unilateral spatial neglect is a neuropsychological syndrome, more frequent after damage to the right cerebral hemisphere, featuring an impaired ability to orient toward the contralateral left side of space and the body, and the inability to detect and report events from that side, of which patients are not aware. In addition to these defective manifestations, patients may show gratuitous behaviors, which include additional productions, unrelated to the task's demand, such as drawings and repeated marks (perseveration) in exploratory target cancellation tasks. Neglect is a multi-component deficit, whose diverse manifestations share a divide between the attended ipsilateral and the neglected contralateral sides of space. Different pathological mechanisms contribute to neglect, including perceptual and premotor impairments, that may be specific to sensory modality, sector of space, and mental images. Neglect may manifest in different coordinate frames with reference to the body and body parts, and objects (egocentric and allocentric neglect). Spatial neglect is a severely disabling disorder, which interferes with functional recovery from stroke. The neural correlates of neglect include cerebral cortical regions surrounding the sylvian fissure: the posterior inferior-parietal cortex, the temporo-parietal junction, the posterior-superior temporal and the frontal premotor cortices, subcortical gray nuclei and white matter fiber tracts connecting these regions. Neglect is independent of, and cannot be traced back to, sensory and motor deficits, and may be interpreted as a derangement of multiple networks, primarily based in the right hemisphere, supporting spatial attention and representation of space and objects in it

Somatoparaphrenia: a body delusion. A review of the neuropsychological literature

A review of published brain-damaged patients showing delusional beliefs concerning the contralesional side of the body (somatoparaphrenia) is presented. Somatoparaphrenia has been reported, with a few exceptions, in right-brain-damaged patients, with motor and somatosensory deficits, and the syndrome of unilateral spatial neglect. Somatoparaphrenia, most often characterized by a delusion of disownership of left-sided body parts, may however occur without associated anosognosia for motor deficits, and personal neglect. Also somatosensory deficits may not be a core pathological mechanism of somatoparaphrenia, and visual field disorders may be absent. Deficits of proprioception, however, may play a relevant role. Somatoparaphrenia is often brought about by extensive right-sided lesions, but patients with posterior (parietal-temporal), and insular damage are on record, as well as a few patients with subcortical lesions. Possible pathological factors include a deranged representation of the body concerned with ownership, mainly right-hemisphere-based, and deficits of multisensory integration. Finally, the rubber hand illusion, that brings about a bodily misattribution in neurologically unimpaired participants, as somatoparaphrenia does in brain-damaged patients, is briefly discussed