Acute perchloroethylene intoxication in an elderly woman: a case report.

BACKGROUND: Perchloroethylene is a colorless, strong-smelling substance commonly used for dry cleaning. Liver and kidney toxicities and carcinogenicity are well-known occupational hazards caused by chronic perchloroethylene exposure. Acute intoxication by ingestion of nondiluted perchloroethylene is rare in the adult population owing to its strong smell and taste. Very few data are available to physicians managing patients in this situation. CASE PRESENTATION: An 89-year-old Caucasian woman accidentally drank perchloroethylene while visiting her laundry, leading to a coma within a few minutes. The poison control center provided little information about perchloroethylene toxicity after ingestion, including an estimated long biological half-life (144 hour) and detrimental effects to liver and kidneys. A long intensive care unit stay was thus expected, potentially leading to several complications. After intubation, transitory hypoxemia appeared and rapidly resolved, while mild hemodynamic instability was managed with fluid resuscitation and anti-arrhythmic drugs. Twelve hours after perchloroethylene ingestion, the patient suddenly woke up and self-extubated. Less than 24 hours after ingestion, she was discharged from the intensive care unit, and 4 days later she was discharged home. CONCLUSION: The patient drank perchloroethylene from a bottle, which prevented her from smelling it, and owing to its taste, only a small sip was likely drunk. However, a much larger intake was presumed, given her rapid and profound central nervous system depression. This case was challenging owing to the paucity of information available regarding acute perchloroethylene ingestion and the duration and magnitude of its effect. The present report will hopefully be of support for clinicians managing patients with this rare acute intoxication.

Determination of cannabinoids in hair: Indicators for illegal vs CBD-rich cannabis use.

Cannabis products rich in cannabidiol (CBD) and low in Δ9-tetrahydrocannabinol (THC) (e.g., light cannabis in Italy) are becoming widely popular and available on the market as replacements for THC preparations and tobacco for their recreational and/or therapeutic benefits. In this paper, which aims to establish alternative discrimination parameters between hair samples from CBD-rich and THC-prevalent cannabis users, cannabinoid concentrations, such as THC, CBD, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) were quantified in 127 hair samples by a GC-MS/MS technique. Initially, this analysis was able to discriminate two cohorts: cohort 1 (individuals with THC values ≥ 0.05 ng/mg and THC-COOH ≥ 0.2 pg/mg or THC-positive users, n = 60) and cohort 2 (individuals with THC values ranging between 0.01 and 0.05 ng/mg and THC-COOH or 11-OH-THC ≥ LOQs, n = 67). The evaluation of CBD/THC ratio in cohort 2 identified two further sub-cohorts 2a (CBD/THC<<1 or ~ 1, THC-prevalent cannabis users) and 2b (CBD/THC>>1, suspected CBD-rich and THC-low cannabis users). The latter showed unusual profiles for THC metabolites, in particular for 11-OH-THC. Statistical evaluation of the data of cohort 1, cohort 2a and cohort 2b yielded significant differences in CBD/THC and THC/11-OH-THC. Based on the analysis of 337 seized cannabis samples and 630 CBD-rich/light cannabis samples by GC-FID and GC-MS, respectively, we also evaluated statistical differences in the CBD/THC ratio between biological (hair) and plant-derived samples. Considering the legal implications of a positive result, the obtained findings could be relevant for the interpretation of cannabinoid concentrations in hair. Further studies are necessary to elucidate the reason behind the unusual metabolic ratios.

Quantitative Lipidomic Analysis of Osteosarcoma Cell-Derived Products by UHPLC-MS/MS.

Changes in lipid metabolism are involved in several pathological conditions, such as cancer. Among lipids, eicosanoids are potent inflammatory mediators, synthesized from polyunsaturated fatty acids (PUFAs), which coexist with other lipid-derived ones, including endocannabinoids (ECs) and N-acylethanolamides (NAEs). In this work, a bioanalytical assay for 12 PUFAs/eicosanoids and 20 ECs/NAEs in cell culture medium and human biofluids was validated over a linear range of 0.1-2.5 ng/mL. A fast pretreatment method consisting of protein precipitation with acetonitrile followed by a double step liquid-liquid extraction was developed. The final extracts were injected onto a Kinetex ultra-high-performance liquid chromatography (UHPLC) XB-C18 column with a gradient elution of 0.1% formic acid in water and methanol/acetonitrile (5:1; v/v) mobile phase. Chromatographic separation was followed by detection with a triple-quadrupole mass spectrometer operating both in positive and negative ion-mode. A full validation was carried out in a small amount of cell culture medium and then applied to osteosarcoma cell-derived products. To the best of our knowledge, this is the first lipid profiling of bone tumor cell lines (SaOS-2 and MG-63) and their secretome. Our method was also partially validated in other biological matrices, such as serum and urine, ensuring its broad applicability as a powerful tool for lipidomic translational research.

LC-MS/MS method development for quantification of doxorubicin and its metabolite 13-hydroxy doxorubicin in mice biological matrices: Application to a pharmaco-delivery study.

This study describes the development of simple, rapid and sensitive liquid chromatography tandem mass spectrometry method for the simultaneous analysis of doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and tissues. The calibration curves were linear over the range 5-250 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in plasma and tumor, over the range 25-500 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in liver and kidney, and over the range 25-1000 ng/mL for doxorubicin and doxorubicinol in urine. The study was validated, using quality control samples prepared in all different matrices, for accuracy, precision, linearity, selectivity, lower limit of quantification and recovery in accordance with the US Food & Drug Administration guidelines. The method was successfully applied in determining the pharmaco-distribution of doxorubicin and doxorubicinol after intravenously administration in tumor-bearing mice of drug, free or nano-formulated in ferritin nanoparticles or in liposomes. Obtained results demonstrate an effective different distribution and doxorubicin protection against metabolism linked to nano-formulation. This method, thanks to its validation in plasma and urine, could be a powerful tool for pharmaceutical research and therapeutic drug monitoring, which is a clinical approach currently used in the optimization of oncologic treatments.