Femoral blood concentrations of the designer benzodiazepine etizolam in post-mortem cases.

Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. To date, there are limited data in the literature to allow for the interpretation of blood concentrations of etizolam in post-mortem cases. A liquid chromatography with tandem mass spectrometry method was used to quantitate etizolam concentrations in 28 post-mortem cases where etizolam was detected. The median concentration of etizolam in femoral blood was 8.5 ng/mL (range 1.0-172.0 ng/mL; n = 24); in antemortem plasma, the etizolam concentration range was 4-44 ng/mL (n = 4). The mean age of the individuals abusing etizolam was 38.5 ± 8.4 years (median 39 years), with the majority being male (86%). In all of the cases, multiple drugs were detected, with the most common being pregabalin (61%) followed by morphine/heroin (54%), diazepam (54%) and benzoylecgonine (21%), illustrating the increasing problem of poly-substance use in drug abusers. The cause of death in the cases in which etizolam was detected was multi-drug toxicity in 87.5% of the cases, with 12.5% unrelated to drug use (hangings and blunt-force trauma). These data will further help forensic practitioners with the interpretation of post-mortem etizolam concentrations.

Post-mortem diagnosis of kidney impairment: An experimental study.

The determination of the role that drugs may have played in a death is an important part of the investigation into unexplained deaths. Renal impairment may lead to a reduction in drug excretion rate and therefore an accumulation of drugs or metabolites, leading to possible toxic or lethal effects. Creatinine levels are known to be stable in the post mortem period and in life can give an indication of kidney function. There are however widely reported limitations when using creatinine in isolation and so we investigated the usefulness of using estimated glomerular filtration rate (eGFR) for scoring an individual as having renal impairment using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. We analysed unpreserved vitreous for creatinine in 812 individuals using an isotope dilution mass spectrometry (ID-MS) traceable enzymatic. We found that the biochemical analysis of post mortem vitreous creatinine and subsequent calculation of eGFR is a useful adjunct to the standard testing that takes place during a post-mortem examination and can assist in death investigation. Using an eGFR of <60 mL/min/1.73 m2 gave a sensitivity of 94.3% and specificity of 97.3% when scoring an individual as having renal impairment. We therefore recommend the calculation of eGFR for the determination of possible renal impairment in post mortem investigations. It is, of course, always pertinent to interpret any results using a wealth of case information. Extreme caution should be exercised in cases where insufficient clinical information/history is available, particularly in cases in which there is suspected diabetic ketoacidosis, dehydration or hospitalisation prior to death.

Comparison of IFCC-calibrated HbA(1c) from laboratory and point of care testing systems.

OBJECTIVE: WHO, IDF and ADA recommend HbA(1c) ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA(1c) from several methods for research relating glycaemic markers. RESEARCH DESIGN AND METHODS: HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000(®)+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol). RESULTS: Median (IQ range) on IFCC SRM was 7.5% (6.8-8.4) (58(51-68) mmol/mol) HbA(1c) with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r(2)=0.984, p<0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r(2)=0.976, p<0.001 with a very small negative difference -0.04%(0.11) (-0.4(1.2) mmol/mol), r(2)=0.992, p<0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000(®)+ analyser -0.13%(0.28) (-1.4(3.1) mmol/mol), r(2)=0.955, p<0.001 and A1cNow+ cartridges -0.70%(0.67) (-7.7(7.3) mmol/mol), r(2)=0.699, p<0.001 (n=113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration. CONCLUSIONS: Small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA(1c) range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.