This paper describes the investigation of synthetic cannabinoid news psychoactive substances in drug rehabilitation patients in the UAE. This represents the latest data for such drugs in the Gulf region.
Background: Vitreous humor (VH) is a specimen of great value in forensic investigations and is being used for evaluating possible post-mortem formation of ethanol. Ethyl glucuronide (EtG) is an ethanol metabolite that has found interest for the same purpose. Both compounds can be measured in VH and because of differences in rate of distribution and elimination they may offer complementary information. Methods: VH, femoral blood (FB) and urine were collected from 117 autopsy cases for forensic investigation. Ethanol was measured with headspace gas chromatography, while EtG was measured with liquid chromatography - tandem mass spectrometry. Results and conclusion: Ethanol was detected in all matrices in 39 cases, while EtG was present in 62 cases. The VH-FB and the VH-urine ethanol concentrations in the 39 cases were statistically correlated (p < 0.00001). In one case with an ethanol concentration of 0.11 g/L in FB, no ethanol was detected in VH and urine, and no EtG in any specimen, indicating a possible post-mortem formation. EtG was present in VH in more cases than in FB and urine. The correlation between the EtG concentrations in VH and FB was statistically significant (p < 0.0003) as was the case also for VH and urine (p < 0.001). The combined information on ethanol and EtG concentrations in the three matrices can be used to interpret alcohol drinking habit before death. This study confirms the value of using VH as a specimen in forensic investigations regarding recent exposure to ethanol. EtG can be used not only for investigating postmortem ethanol formation but also for estimating recent alcohol drinking. (C) 2020 Published by Elsevier B.V.
This study aimed to determine whether hydromorphone and codeine can be detected in oral fluid specimens following administration of Substitol™, a slow-release formulation of morphine. This is of interest for those monitoring treatment compliance using drug testing. Oral fluid specimens collected for compliance assessment in routine clinical practice or as part of a clinical trial were subjected to quantitative analysis of hydromorphone, morphine, codeine, and 6-acetylmorphine using highly sensitive mass spectrometric methods. Oral fluid was collected using a Greiner Bio-One saliva collection system. Patients undergoing substitution treatment with Substitol™, methadone, or buprenorphine were included, together with patients undergoing pain treatment with hydromorphone. Hydromorphone was detected in 642 of the 663 (97%) samples from substitol-treated patients. Concentrations were not higher in methadone- and buprenorphine-treated patients who relapsed into heroin use, or in patients on hydromorphone therapy. Codeine was detected in 29% of the samples. These concentrations were lower than those in patients who had relapsed to heroin use. Clinical administration of morphine can lead to detectable concentrations of both hydromorphone and codeine in oral fluids. This should be taken into consideration when using drug testing in oral fluid samples for compliance assessment in this patient group.
The diester-diterpene alkaloid aconitine was quantified by liquid chromatography-tandem mass spectrometry in post-mortem specimens of three cases where suicidal ingestion of Aconitum napellus L. ('monkshood') was supposed. In an attempt at rationalization, sample preparation and chromatographic conditions of plasma/serum drug analysis routine were utilized. Linearity was established from 0.5 to 20 µg L⁻¹ using newborn calf serum (NCS) as a surrogate calibration matrix for all sample types and mesaconitine as an internal standard. Validation (selectivity, sensitivity, precision, accuracy, recovery of the extraction procedure, matrix effect, processed sample stability) confirmed the applicability of the analytical method to various post-mortem matrices. Internal standard selection was based on multi-matrix process efficiency data. In human post-mortem peripheral blood a lower limit of quantification of 0.51 µg L⁻¹ and a limit of detection of 0.13 µg L⁻¹ were accomplished (0.1 ml sample aliquots). Aconitine was degraded to a large extent in different sample types when being stored at +20 °C for 30 days, while at -20 °C and for some matrices also at +4 °C no appreciable degradation occurred. Aconitine concentrations in real samples were 10.3-17.9 µg L⁻¹ (peripheral blood, n = 3), 14.9-87.9 µg L⁻¹ (heart blood, n = 3), 317-481 µg L⁻¹ (urine, n = 2), 609-4040 µg L⁻¹ (stomach content, n = 3), 139-240 µg L⁻¹ (bile, n = 2), 8.4 µg L⁻¹ (vitreous humor, n = 1), 54.7 µg L⁻¹ (pericardial fluid, n = 1), 492 µg kg⁻¹ (liver, n = 1), 15.2-19.7 mg L⁻¹ (unknown liquids secured onsite, n = 3). Together with concomitant circumstances the analytical data provided compelling evidence for acute Aconitum poisoning as being the cause of death.
Acetaldehyde is a strongly electrophilic compound that is endogenously produced as a first intermediate in oxidative ethanol metabolism. Its high reactivity towards biogenic nucleophiles has toxicity as a consequence. Acetaldehyde readily undergoes a non-enzymatic condensation reaction and consecutive ring formation with cysteine to form 2-methylthiazolidine-4-carboxylic acid (MTCA). For analytical purposes, N-acetylation of MTCA was required for stabilization and to enable its quantification by reversed-phase chromatography combined with electrospray ionization–tandem mass spectrometry. Qualitative screening of post mortem blood samples with negative blood alcohol concentration (BAC) mostly showed low basal levels of MTCA. In BAC-positive post mortem samples, but not in corresponding urine specimens, strongly increased levels were present. To estimate the association between ethanol consumption and the occurrence of MTCA in human blood, the time curves of BAC and MTCA concentration were determined after a single oral dose of 0.5 g ethanol per kilogram of body weight. The blood elimination kinetics of MTCA was slower than that of ethanol. The peak concentration of MTCA (12.6 mg L-1) was observed 4 h after ethanol intake (BAC 0.07‰) and MTCA was still detectable after 13 h. Although intermediary acetaldehyde scavenging by formation of MTCA is interesting from a toxicological point of view, lack of hydrolytic stability under physiological conditions may hamper the use of MTCA as a quantitative marker of acetaldehyde exposure, such as resulting from alcohol consumption.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of the ethanol consumption markers ethyl glucuronide (EtG), ethyl phosphate (EtP), and ethyl sulfate (EtS) in human urine was developed. A reversed-phase/weak anion exchange type stationary phase demonstrated particular suitability for the analysis of these highly polar acids. Sample preparation was minimized to centrifugation and dilution of urine prior to injection. The method was validated in the range of 5-750 microg.L(-1) with 1:20 and 1:1000 diluted urine, which corresponds to actual concentration ranges of 0.1-15 and 5-750 mg.L(-1) in undiluted samples. Method validation was carried out using six different lots of human urine. Over the entire calibration range intraday and interday precision (each n = 5, three concentration levels per dilution factor) adopted values between 0.6 and 4.7% and 0.8 and 12.1%, relative standard deviation, respectively. Corresponding accuracy values ranged between 94.2 and 113.5% and 86.6 and 110.9%, respectively. Matrix effects (absolute/relative) were found to be present in minor extent (approximately -30% to +15% MS/MS signal alterations) and were well corrected by the employed isotopically labeled internal standards. The validated assay was applied to urine samples of a drinking study as well as postmortem specimens. It was possible to assess the principal potential of EtP as ethanol consumption marker. Elevated concentration levels were found in real samples; however, EtP seems to be less sensitive compared to the previously known ethanol phase II conjugates EtG and EtS.
A CE method for the determination of the ethanol consumption marker ethyl sulfate (EtS) in human urine was developed. Analysis was performed in negative polarity mode with a background electrolyte composed of 15 mM maleic acid, 1 mM phthalic acid, and 0.05 mM cetyltrimethylammonium bromide (CTAB) at pH 2.5 and indirect UV detection at 220 nm (300 nm reference wavelength). This buffer system provided selective separation conditions for EtS and vinylsulfonic acid, employed as internal standard, from urine matrix components. Sample pretreatment of urine was minimized to a 1:5 dilution with water. The optimized CE method was validated in the range of 5700 mg/L using seven lots of urine. Intra- and inter-day precision and accuracy values, determined at 5, 60, and 700 mg/L with each lot of urine, fulfilled the requirements according to common guidelines for bioanalytical method validation. The application to forensic urine samples collected at autopsies as well as a successful cross-validation with a LC-MS/MS-based method confirmed the overall validity and real-world suitability of the developed expeditious CE assay (sample throughput 130 per day).