Complete investigations (autopsy, toxicology, and histology) in a death due to apixaban overdose.

The dead body of a 54-year-old man was found at home by his partner. He was off work due to depression. A letter with suicidal intention was present on the scene. He was known to be a heavy drinker, and near the body, an empty bottle of whisky was found. In addition, 2 empty blisters of Eliquis (apixaban) 5 mg, corresponding to 40 tablets, were identified. Apixaban is an oral anticoagulant, acting as a factor Xa inhibitor. Autopsy findings were mostly unremarkable, except numerous bruises and some superficial self-inflected wounds. Histology showed hematomas of calyces and renal pelvis and in the liver, several areas of perivenular haemorrhagic necrosis. Others organs were congestive. Femoral venous blood alcohol was 0.11 g/L. In femoral venous blood, a toxic concentration of apixaban was measured at 1184 ng/mL using LC-MS/MS. Other drugs found at therapeutic concentrations included diazepam (99 ng/mL), nordiazepam (171 ng/mL), flecainide (447 ng/mL), and mianserine (65 ng/mL). Using liquid chromatography coupled to high-resolution mass spectrometry, 2 metabolites were identified, O-desmethyl-apixaban (61.8% of the apixaban response) and hydroxyl-apixaban (4.5% of the apixaban response). Long-term therapy was confirmed by a concentration of 10390 pg/mg in pubic hair.

Analysis of Cocaine and Its Metabolites in Urine after Consumption of Coca Tea by Five Subjects and Subsequent Hair Testing.

Coca tea is a popular drink in some countries of South America where it is reputed to have medicinal properties. This preparation is composed of natural cocaine (COC) alkaloids and therefore can be banned in some countries. During an anti-doping control in Peru the urine of an athlete tested positive for benzoylecgonine (BZE) ecgonine methyl ester (EME) and COC (400 180 and 0.5 ng/mL respectively). The athlete indicated that she had consumed coca tea in the morning before the competition. As her lawyer contacted us to assess the scientific aspects of the possible involvement of coca tea to explain the adverse analytical finding a study was implemented with similar tea bags urine specimens were collected for each subject for 3 days to follow the elimination of COC and metabolites (BZE and EME). All samples were analyzed byultra high performance liquid chromatography tandem mass spectrometry after alkaline extraction. Maximum detection times for COC was 20 h with concentrations ranging from 6 to 91 ng/mL. Maximum detection times for BZE and EME were 70 h and 60 h respectively with concentrations ranging from 6 to 3,730 ng/mL and from 6 to 1,738 ng/mL. The concentration profiles were identical for the five volunteers. This study supports the athlete's claims. In addition, the sample of hair strands of the five subjects was collected a month later and all the hair tests showed a negative result for COC with a limit of decision of 10 pg/mg. Although it is accepted that a 4 mg dose of COC has no significant pharmacological effect the consumption of coca tea can lead to significant legal consequences since the measured urine concentrations sometimes cannot be considered incidental. Therefore, discrimination between coca tea consumption and recreational COC abuse relies primarily on hair analysis.

Interpretation of Cannabis Findings in the Hair of Very Young Children: Mission Impossible.

BACKGROUND: Hair has been suggested since the middle of the 90's to be a suitable matrix to document repetitive exposure to cannabis. Because it is possible to detect Δ9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) in cannabis smoke, the identification of the metabolite, 11-nor-Δ9-tetrahydrocannabinol carboxylic acid (THC-COOH) has been considered to allow the discrimination of active use. OBJECTIVE: Although the identification of an active compound in a child's hair shows contamination of the local environment, it is a challenge to discriminate between hair incorporation after ingestion or inhalation and environmental external deposition from dust, smoke, or even contaminated surfaces by hand contact. However, it is particularly important in case of children to correctly interpret the data, particularly for a realistic assessment of the health risk. We present here a series of hair tests for cannabis where the interpretation was almost impossible to establish. METHOD: Hair specimens were collected during the autopsy of the 12 children, aged 2 to 24 months, either deceased from shaken baby syndrome (SBS, n=4), mechanic asphyxia (MA, n=1) or sudden infant death (SID, n=7) during January 2015 to April 2017. After decontamination, the hair specimens were tested for THC, CBN and CBD and THC-COOH. The whole length of hair was submitted to analysis. RESULTS: The amount of hair from children can be as low as 8 mg. This may affect the limit of quantitation of all drugs, but particularly THC-COOH. Eight from twelve hair tests were positive for cannabis markers, i.e. THC (39 to 1890 pg/mg, n=8), CBN (< 5 to 1300 pg/mg n=8), CBD (10 to 2300 pg/mg, n=8) and THC-COOH (not detected to < 0.5 pg/mg, n=5). In 4 cases from 8 positive findings, it was not possible to test for THC-COOH (not enough material). CONCLUSION: Establishing a window of detection when testing for drugs in young children is a very complicated task. Hair from children is finer and more porous in comparison with adult (the risk of contamination from sweat and environmental smoke is higher than in adults). The final interpretation of cannabinoid findings in the children's hair is very complicated as this can result from in utero exposure (although none of the mother admitted cannabis use during pregnancy), oral cannabis administration by the parents to achieve sedation, close contact to cannabis consumers (hands, bedding, dishes) and inhalation of side-stream smoke. Over-interpreting cannabis findings in hair can have very serious legal implication in child protection cases. Practicing scientists have the responsibility to inform the child protection authorities, courts, etc. about these limitations.