Effectiveness of a Reliable Toxicological Analysis for a Correct Diagnosis of Acute Intoxication in Pediatrics: 2-Year Experience of an Analytical Toxicological Laboratory.

OBJECTIVES: This study aimed to assess the role of the laboratory of toxicology as a support for a correct diagnosis of intoxication through the application of a reliable analytical approach, critically designed to meet pediatric needs. METHODS: Data collected from 360 cases of suspected intoxications in pediatric patients (aged 1 day to 17 years) during the period 2018 to 2019 are presented. Toxicological analyses were performed through different techniques (immunoassay and chromatography) with parameters (limit of detection and cut-off) adjusted according to pediatric needs to produce reliable toxicological data for a wide number of prescription drugs, drugs of abuse, and poisons. RESULTS: We present results about (1) agents involved in suspected poisonings and the methods adopted for a definite analytical diagnosis, (2) the assessment of the concordance of results for analyses proceeded by different techniques, and (3) the percentage of agreement between analytical result and clinical suspicion. CONCLUSIONS: An analytical approach critically designed to minimize misinterpretation of laboratory data and able to provide reliable results for a wide number of substances in a time compatible with the urgency represents a useful support for a correct diagnosis of intoxication in pediatrics.

Prevalence of Stimulant, Hallucinogen, and Dissociative Substances Detected in Biological Samples of NPS-Intoxicated Patients in Italy.

A number of new psychoactive substances (NPS) have been released in the last decade, and the list of NPS continues to grow. This paper reports a retrospective evaluation of the toxicological analyses in 1,445 suspected intoxication cases by psychostimulant, hallucinogen, and dissociative NPS occurring in hospitals across Italy from 2011 to 2019. The objectives of the study were to contribute to the monitoring of the NPS diffusion based on analytically confirmed intoxications, and to evaluate the importance of the clinical toxicological laboratory in the diagnosis of NPS intoxication. For at least one NPS of the considered classes, 246 patients (17.0%) tested positive. Forty-four different NPS were detected and a consistent turnover was observed during the nine-year period, especially regarding cathinones. Among the positive cases, 47.2% tested positive for dissociative NPS, with particular regard to ketamine. Hallucinogens (30.9%) was the second most frequent NPS involved. Stimulants were found in 20% of the positive cases with a considerable presence of cathinones. Findings confirm the dynamism of the NPS phenomenon, underline the importance of awareness of this new public health threat among health care professionals, and highlight the need for analytical confirmation for the identification of the drugs in forensic contexts.

Analytically Confirmed Intoxication by 4-Fluoromethylphenidate, an Analog of Methylphenidate.

4-Fluoromethylphenidate (4F-MPH) is an halogenated derivative of methylphenidate (MPH), a re-uptake inhibitor for dopamine and norepinephrine used for the treatment of attention deficit hyperactivity disorders. In the last few years, several compounds structurally related to MPH have been marked as new psychoactive substances (NPS) with stimulating and euphoric effects similar to the parent drug, but with more dopaminergic activity. This report represents the first case of an analytically confirmed non-fatal intoxication by 4F-MPH. A 26-year-old female was admitted to the emergency department with neuropsychiatric and cardiologic symptoms that lasted for a week, during which she sniffed a powder named 4F-MPH acquired as entactogen on the Internet. The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. The seized product was analytically characterized by gas chromatography-mass spectrometry, liquid chromatography high-resolution mass spectrometry and nuclear magnetic resonance. These analyses confirmed the composition of the product as a 4F-MPH diastereomeric (±)-threo and (±)-erythro mixture, with a large preponderance of the active (±)-threo isomer. A minimal validation, intended for rare analytes, was performed for the quantification of 4F-MPH in the biological samples by liquid chromatography-tandem mass spectrometry. Accuracy (bias) and precision were within ±15% for both blood and urine. The blood and urine concentration of (±)-threo 4F-MPH were 32 ng/mL and 827 ng/mL, respectively. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only.

Illicit drugs in Emergency Department patients injured in road traffic accidents.

Urine and blood samples from 1730 drivers involved in road accidents (July 2012 - December 2015) were analyzed for the evaluation of driving under influence of drug of abuse according to the Lombardia Region guideline. The 22.5% (95% CI 20.5 to 24.5) of urine screenings tested positive for at least one class of drugs. 10.6% (95% CI 9.2 to 12.1) of the 1730 drivers were under the influence of drug, being blood concentration above the cut-off limit for at least one active substance; the proportion of illicit drugs in blood was cocaine 5.7 % (95% CI 4.7 to 6.9), cannabinoids 3.7 % (95% CI 2.9 to 4.7), opiates 1.4% (95% CI 0.9 to 2.1), methadone 1.4% (95% CI 0.9 to 2.1), amphetamines 0.2% (95% CI 0.04 to 0.5). Trend in proportion showed similar percentage (about 5%) of cocaine and cannabinoids consumption in the last two years. Poly-drug of abuse consumption emerged in the 10.4% (95% CI 6.4 to 15.7) of the positive blood and alcohol was above the legal limit in 47% (95% CI 39.6 to 54.5) of the subjects driving under the influence of drugs.

MAM-2201 (analytically confirmed) intoxication after "Synthacaine" consumption.

Excitatory behavior, xerostomia, chest pain, severe dyspnea, tachycardia (150 beats/min), and mild hypertension (160/80 mm Hg) without ECG abnormalities were observed in a 20-year-old subject 6 hours after nasal insufflation (snorting) of a "legally" obtained white powdered substance sold as Synthacaine. A serum sample was found to contain MAM-2201 (11 ng/mL), a synthetic cannabinoid receptor agonist, and benzocaine. The patient's symptoms improved after administration of diazepam and intravenous fluids. Synthacaine was sold as legal cocaine, suggesting the user can expect an effect like that of cocaine. The pharmacologic receptor profile and chemical structure of MAM-2201 is similar to the synthetic cannabinoid receptor agonists AM-2201 and JWH-122 (2 potent synthetic cannabinoid receptor agonists with high affinity to cannabinoid receptors).

Behavioral responses to acute and sub-chronic administration of the synthetic cannabinoid JWH-018 in adult mice prenatally exposed to corticosterone.

Recent data indicate that both availability and consumption of synthetic and natural psychoactive substances, marketed under the name of "legal highs", has increased. Among them, the aminoalkylindole-derivative JWH-018 is widely distributed due to its capability of binding the cannabinoid receptors CB1 and CB2 thereby mimicking the effects of classical drug agonists. To address whether the behavioral effects of the synthetic compound JWH-018 are similar to those induced by classical cannabinoid agonists, we investigated, in outbred CD1 mice, the consequences of its acute and sub-chronic administration (0, 0.03, 0.1, or 0.3 mg/kg, IP) at the level of body temperature, pain perception, general locomotion, and anxiety. In order to address whether the exposure to precocious stressors-modified individual reactivity to this psychoactive substance, we also investigated its effects in adult mice previously exposed to prenatal stress in the form of corticosterone supplementation in the maternal drinking water (33 or 100 mg/L). In the absence of major effects on motor coordination, JWH-018-reduced body temperature, locomotion and pain reactivity, and increased indices of anxiety. Prenatal corticosterone administration-reduced individual sensitivity to the effects of JWH-018 administration in all the aforementioned parameters. This altered response is not due to variations in JWH-018 metabolism. Present data support the hypothesis that precocious stress may affect, in the long-term, the functional status, and reactivity of the endocannabinoid system.