Cannabis intoxication after accidental ingestion in infants: urine and plasma concentrations of Δ-9-tetrahydrocannabinol (THC), THC-COOH and 11-OH-THC in 10 patients.

Introduction: Accidental cannabis poisoning after oral ingestion in infants is an emerging cause of intoxication with well-known clinical aspects but few data exist regarding the levels of cannabinoids in plasma and urine. Here, we present data on the concentrations of Δ-9-tetrahydrocannabinol (THC) and metabolites in plasma and/or urine in 10 infants after cannabis intoxication.Materials and methods: Cannabinoids were detected using an automated immunochemical method and quantified using liquid chromatography coupled with mass spectrometry.Results: Ten infants were admitted after cannabis poisoning. THC, THC-COOH and 11-OH-THC plasma levels ranged from 4.4 to 127 ng/mL, from 28 to 433 ng/mL and from 2 to 59.8 ng/mL, respectively. THC-COOH urine levels ranged from 748 to 5689 ng/mL. The most common symptoms were drowsiness, hypotonia, behavioural disorder and tachycardia.Discussion: No correlation between plasma concentrations and symptoms could be found, but the concentration of THC-COOH in the two patients who experienced seizures was higher than 3000 ng/mL. This series of cases of accidental intoxication in infants showed high THC and metabolites concentrations in urine and plasma.

[Accreditation of the toxicological screening: recommendations of the SFBC-SFTA group]. / Accréditation du criblage toxicologique : recommandations du groupe SFBC-SFTA.

Toxicological screening is a specific approach to analytical toxicology that uses analytical tools such as GC-MS, LC-UV (diode array) or LC-MS. Toxicological screening allows the detection and simultaneous identification of a large number of compounds. The results may be based on the use of one or more techniques. As part of the accreditation process for medical biology examinations according to standard NF EN ISO 15189, the group from SFTA and SFBC recommends an approach to accredit toxicological screening. Indeed, the complexity of the accreditation of this analysis comes in particular from the high number of compounds that can be detected. Validation parameters are discussed in the specific context of toxicological screening by considering two distinct approaches: the simple identification of compounds, or the identification and estimation of a range of concentration related to clinical outcomes.

A Severe Neonatal Lymphopenia Associated With Administration of Azathioprine to the Mother in a Context of Crohn's Disease.

Azathioprine is commonly used in Crohn's disease. It has been administered to many pregnant women over many years without significant side effects. However, pancytopenia and severe combined immune deficiency-like disease have been reported in infants whose mothers received azathioprine throughout pregnancy. Moreover, myelotoxicity has been described in patients being treated with azathioprine and having a low or absent thiopurine S-methyl transferase [TPMT] activity.Here, we describe the case of a newborn girl found to be highly lymphopenic [< 300 CD3+ T cells] after a positive newborn screening for severe combined immuno deficiency. The clinical examination was normal. The mother was treated with azathioprine throughout her pregnancy, without any reduction of the dose. It was shown that the mother was heterozygous for the 3A [TPMT] activity mutation and that the baby was homozygous for the same mutation; 6-thioguanine nucleotides were high (744 pmol/8.108 red blood cells [RBC]) in the mother and detectable in the infant [177 pmol/8.108 RBC].Although rare, this case illustrates the potential grave consequences of unsuspected TPMT homozygosity in a newborn of a mother receiving thiopurines during pregnancy. Because of the severity of the risk for the newborn, consideration should be given to performing maternal genetic testing and newborn routine blood count in cases of thiopurine treatment during pregnancy.

Evaluation of a Methotrexate Chemiluminescent Microparticle Immunoassay: Comparison to Fluorescence Polarization Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry.

OBJECTIVES: For most laboratories, methotrexate (MTX) concentrations are routinely monitored by fluorescence polarization immunoassay (FPIA). In anticipation of an announced withdrawal of the FPIA reagent on the Abbott TDxFLx (Abbott Diagnostics, Abbott Park, IL), we have evaluated a new reagent kit developed by Abbott on the Architect i1000, based on chemiluminescent microparticle immunoassay (CMIA). METHODS: Precision, inaccuracy, and selectivity were assessed. Interassay variability was established using 75 plasma patient samples treated with MTX and analyzed by two methods: FPIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS FOR MTX,: the intraday inaccuracy was between -6.37% and +3.52%, while interday performance was between -3.70% and 7.90%. Intraday and interday imprecision was less than 2.65% and less than 2.22%, respectively. The correlation coefficient between CMIA and FPIA or LC-MS/MS was 0.9969 and 0.9985, respectively. CONCLUSIONS: These results comparing CMIA vs FPIA and LC-MS/MS indicate that CMIA is a suitable alternative to the FPIA method.

Comparison Between an Automated and Manual Extraction for the Determination of Immunosuppressive Drugs Whole Blood Concentrations by Liquid Chromatography Tandem Mass Spectrometry.

BACKGROUND: The whole blood extraction for liquid chromatography tandem mass spectrometry (LC-MS/MS) of simultaneous quantification of cyclosporine A (Cys A), tacrolimus (Tacrs), sirolimus (Siros), and everolimus (Evers) is still performed manually in many laboratories. The analytical results obtained with an automated method using a liquid handler versus a classical manual preparation were compared. METHODS: Cys A (n = 36), Tacrs (n = 50), Siros (n = 34), Evers (n = 38) whole blood samples of patients were analyzed by LC-MS/MS assay after manual preparation and automated process using a liquid handling platform including a centrifugation step. RESULTS: The comparison between manual and automated extraction investigated by a linear regression showed a high correlation between results [(Tacrs "automated") = 1.0927 × (Tacrs "manual") - 0.36; (Cys A "automated") = 1.0284 × (Cys A "manual") + 0.0312; (Siros "automated") = 0.9923 × (Siros "manual") + 0.4001; (Evers "automated") = 1.0000 × (Evers "manual") - 0.0600]. CONCLUSION: The results obtained by the automated and manual preparation are consistent. The automated method is applied for high-throughput therapeutic drug monitoring of immunosuppressive drugs in routine practice, leading to an increase in quality.

Fatal anoxia due to rachacha consumption: Two cases reported.

Deaths due to ingesting rachacha, which is a homemade paste obtained by decocting poppy heads, are very rare. No fatalities have been recorded in scientific publications. This product is not considered to be very dangerous by its users. We are reporting the first deaths (a 30-year-old man and a 28-year-old woman), after ingesting rachacha balls and alcohol consumption during an evening with a friend. Signs compatible with acute anoxia were observed during autopsy. Toxicological analyses highlighted the presence of morphine and codeine in the blood, urine and bile, with an absence of 6-acetylmorphine. Concomitant consumption of alcohol certainly played a role in the occurrence of death. The black paste found at the scene was identified as rachacha. The mean of consumption (orally) was confirmed by the presence of morphine and codeine in the gastric contents of both victims. The analysis of hair samples was performed to reveal the substance consumption history. Therefore, a possibility of contamination by sweat and/or putrefactive liquids in the post-mortem period must be considered for the interpretation of the results. These two cases show that taking rachacha can be dangerous, especially when combined with the consumption of substances which could potentiate respiratory depression induced by morphine.