We used gas chromatography-chemical ionization mass spectrometry with selected ion monitoring of the (M-59)+ ions to determine polyols (as their peracetyl derivatives) in serum. The internal standard was 2-deoxygalactitol. Mean (and SD) polyol concentrations (mg/L) in 33 normal sera were: erythritol 0.45 (0.14), threitol 0.20 (0.06), adonitol 0.06 (0.02), arabinitol 0.37 (0.12), xylitol 0.05 (0.02), mannitol 0.41 (0.45), galactitol 0.15 (0.11), sorbitol 0.16 (0.11). Arabinitol determined in the same 33 normal sera by trimethylsilylation was 0.39 (0.13) mg/L. In 32 samples from cancer patients with normal creatinine, all polyol concentrations were in the normal range except for seven increased erythritol and one increased threitol concentrations. In all six patients with renal dysfunction we found increased erythritol and arabinitol, and increased threitol and mannitol in four of the six. Initial results showed that only arabinitol concentrations increased in invasive candidiasis.
Background AMB-FUBINACA is a synthetic cannabinoid that has been associated with periodic outbreaks of acute poisonings, but few fatalities. In late May, June and July 2017 Auckland, New Zealand, experienced an outbreak of deaths associated with AMB-FUBINACA that continued at a rate of about 2–3 per month through February 2019. The aim of this study was to define the demographic, circumstantial, pathological and toxicological characteristics of this outbreak. Methods All records of the Northern Forensic Pathology Service, Auckland Hospital, were reviewed in which the word “AMB-FUBINACA” was referenced, including initial police reports, autopsy reports and toxicology reports. Recorded data included age, sex, race/ethnicity, times and locations, cause of death, autopsy and toxicology findings, and a brief summary of the circumstances of death. Descriptive statistics were performed using IBM® SPSS® Statistics Version 24 and Microsoft® Excel® Version 14.7.2. Findings Sixty-four cases were identified. One sudden infant death and five cases where cause of death was due to trauma were excluded. Of the remaining 58 cases, 88% were male. Mean age was 42 years. In 95% of the deaths, AMB-FUBINACA alone or in combination with alcohol or another drug was listed as the primary or contributory cause of death. In 41 cases postmortem blood concentrations of AMB-FUBINACA acid were available, ranging from <45 ng/mL to >1000 ng/mL, mean 229 ng/mL, median 140 ng/mL. Comorbidities identified included mixed intoxications (29%), heart disease (47%) and obesity (16%). A mental health diagnosis was reported in 50%, and 40% were on antipsychotic medications. Interpretation This study presents characteristics, comorbidities and toxicological findings in a unique outbreak of deaths associated with the synthetic cannabinoid AMB-FUBINACA in Auckland, NZ. Funding All work was funded as part of the usual employment of the authors in their respective institutions. No special funding sources are reported.
Sodium valproate at a concentration of 300 mumol/l in whole blood, partitioned between the red blood cell and plasma to produce a red blood cell/plasma partition ratio of 0.20. Red blood cell uptake was proportional to percent free drug in plasma and uptake was maximal when plasma was replaced by buffer, producing a red blood cell/buffer ratio of 0.87. Reduction of plasma protein binding by plasma dilution, by increasing the total sodium valproate plasma concentration, or by renal or hepatic disease in 24 patients, caused a predictable rise in red blood cell uptake of drug. The red blood cell represented a relatively small compartment for free sodium valproate in blood, however uptake of the drug into this compartment increased considerably in states of reduced plasma protein binding. Because the concentration of drug in the red blood cell reflects free drug concentration in plasma, the red blood cell may serve as an indicator of free drug changes in blood.
We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs-of-abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs-ofabuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported-liquid-extraction (SLE) followed by liquid chromatography −tandem mass spectrometry (LC−MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante-and post-mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB-FUBINACA and/or acid (61%), 5F-ADB and/or acid (40%), ADB-FUBINACA (11%), 5F-MDMB-PICA acid (6%), and MDMB-FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.
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