Journal of analytical toxicology最新文献

The long-term stability of drug concentrations in human plasma samples when stored under normal laboratory conditions over several years is important for research purposes and clinical re-evaluation, but also for forensic toxicology. Fifty human plasma samples from a former clinical trial were re-analyzed after storage at -20°C for 11 years. Plasma samples were extracted using solid-phase extraction. Isotope labelled sufentanil-D5 was used as internal standard. Sufentanil plasma concentrations were determined by ultra-performance liquid chromatography (UPLC) with gradient elution, followed by tandem mass spectrometry with electrospray ionization. The linear dynamic range (LDR) was 25 - 2500 pg/mL, the limit of detection was 10 pg/mL, and the lower limit of quantification was 25 pg/mL. Intra- and inter-assay error did not exceed 6%. The deviation of the measured sufentanil plasma concentrations between the reanalysis and the first analysis was -63 ± 14% (mean ± SD). Therefore, sufentanil concentrations in human plasma were not stable in samples frozen at -20°C over 11 years.

The identification of novel psychoactive substances (NPSs) in casework at the Los Angeles County Department of Medical Examiner (LACDME) is constantly evolving. The case detailed herein marks the first detection of metonitazene in forensic casework at the LACDME which occurred in August 2023. Furthermore, bromazolam was found in the decedent's system and both substances were identified in drug evidence collected at the death scene. No other drugs were detected and the manner and cause of death were determined as accidental due to effects of bromazolam and metonitazene. The concentrations detected were 1.6 ng/mL and 4.4 ng/mL of metonitazene in the jugular blood and femoral blood, respectively, and 93 ng/mL of bromazolam in the femoral blood. Constraints in screening techniques conducted by toxicology laboratories create challenges in which numerous NPSs available on the illicit drug market can go undetected. Even if labs detect an NPS in their screening methodology, confirmation methods might not cover every NPS, given the impracticality of labs keeping pace with validations as new NPSs emerge in casework. The significance of testing medical evidence collected at death scenes by drug chemistry analysis becomes crucial when initial toxicology results are negative. In cases where there is evidence of potential drug paraphernalia this is especially true as it can be pivotal in determining the cause and manner of death.

Aim: This study focused on the simultaneous detection of amphetamine, 3,4-methyl enedioxy methamphetamine, morphine, benzoylecgonine, and 11-nor-9-carboxy- tetrahydrocannabinol (Δ9-THC-COOH) in whole blood and DBS. It is aimed to select a solvent mixture for liquid-liquid extraction (LLE) technique employing LC-MS/MS. The obtained DBS results were compared with the whole blood samples results.

Methods: A simple, rapid, and reliable LC-MS/MS method was developed and validated for all analytes in whole blood and DBS. LC was performed on a Hypersil Gold C18 column an initial step with a gradient of 0.01 % formic acid, 5 mM ammonium format buffer in water, and acetonitrile at 0.3 ml/min with 7.5-min runtime.

Results: A methanol:acetonitrile (40:60 v/v) mixture was selected for both matrices. LOQ values were 10-25 ng/mL; linear ranges were LOQ-500 ng/ml for all analytes; correlation coefficients were greater than 0.99, and all calibrator concentrations were within 20%. Analytical recovery in blood and DBS ranged from 84.9-113.2% of the expected concentration for both intra and-inter day. Analytes were stable for 1, 10, and 30 days after three freeze/thaw cycles. It was determined that the variances of the results obtained with the two matrices in the comparison study were equal for each analyte, and the results were highly correlated (r=0.9625).

Conclusion: A sensitive, accurate, and reliable chromatographic method was developed to determine amphetamine, MDMA, morphine, benzoylecgonine, and cannabis, by performing the same preliminary steps with whole blood and dried blood spots. It was observed that the results obtained in these two matrices were compatible and interchangeable when statistically compared.

Recently, etomidate has been widely used as an alternative in illicit drug market. It is usually added to regular cigarette tobacco (commonly known as "cigarette powder") or mixed in e-cigarette oil sold through the Internet, retail stores, or entertainment outlets and other channels. An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed to quantify etomidate and etomidate acid in human blood and urine. The limit of detection (LOD) of etomidate and etomidate acid in blood are 0.5 ng/mL and 2 ng/mL, respectively, and the lower limit of quantification (LLOQ) are 1 ng/mL and 5 ng/mL, respectively. The LOD of etomidate and etomidate acid in urine are1 ng/mL and 2 ng/mL, respectively, and the LLOQ are 2 ng/mL and 5 ng/mL, respectively. The precision, accuracy, recoveries and matrix effects of etomidate and etomidate acid determinations in blood and urine met the requirements for methodological validation. The method was successfully applied to the identification and quantification of etomidate and etomidate acid in blood and urine of 62 forensic cases. The concentration of etomidate ranged from 1.52 to 8.41 ng/mL (positive cases, n=5) and the concentration of etomidate acid ranged from 2.76 to 112 ng/mL (positive cases, n=5) in blood. The concentrations of etomidate and etomidate acid in urine samples were 2.64-79,300 ng/mL (positive cases, n=59) and 6.11-518,000 ng/mL (positive cases, n=60), respectively. Therefore, the concentration of etomidate in blood and urine is mostly higher than that of etomidate.

In recent years the use of 2-benzylbenzimidazole opioids ('nitazenes') has increased with them becoming one of the most prominent synthetic opioid subclasses of novel psychoactive substances. With the increased prevalence there is also a concern of the dangers to public health with the use of nitazenes due to their high potency especially with polypharmacy. To aid in the detection of such compounds it is important that forensic toxicology laboratories maintain up-to-date compound libraries for drug screening methods and that sensitive analytical instrumentation is available to detect the low blood/plasma concentrations of more potent drugs. This includes not only the compounds themselves but also potential metabolites and/or degradation products. Metonitazene is a 'nitro-nitazene' with a nitro group at position 5 of the benzimidazole ring. As a nitro-nitazene there is a potential for bacterial degradation of metonitazene to 5-aminometonitazene, as occurs with nitro-benzodiazepines. In this study we provide evidence from a post-mortem case of degradation of metonitazene in unpreserved post-mortem blood using LC-QQQ-MS, and putative identification of the degradation/ metabolic products 5-aminometonitazene and 5-acetamidometonitazene by LC-QTOF-MS. The results from LC-QQQ-MS analysis indicated that there did not appear to be such degradation in preserved (fluoride/oxalate) blood. These results suggest that nitro-nitazenes may be subject to similar in vitro stability/degradation issues as nitro-benzodiazepines. These breakdown products should be added to instrument libraries to aid in the detection of the use of nitro-nitazenes, and nitro-nitazenes should be quantified in preserved blood samples where available.

The designer benzodiazepine bromazolam is increasingly encountered in forensic casework, including impaired driving investigations. A series of suspected impaired driving cases that tested positive for bromazolam are described herein along with information about driving performance, driver appearance and observed behavior. Bromazolam was indicated in casework either through screening by liquid chromatography time of flight mass spectrometry (LC-TOF/MS) and/or a positive benzodiazepine immunoassay screen. Blood samples were forwarded for quantitative confirmatory analysis using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method with a reporting limit of 2.0 ng/mL. Bromazolam was reported in 98 impaired driving cases from samples reported between January 2021 and December 2023, with the earliest detection from September 2020. Mean and median blood concentrations were 125 ± 145 ng/mL and 84 ng/mL respectively, with a range of 4.2 - 990 ng/mL. Additional positive findings were reported in almost all cases, with the highest result (990 ng/mL) being the only case in which bromazolam was the only finding. Fentanyl was the most frequent drug found in combination with bromazolam. Driving behaviors reported in these cases included erratic driving, errors in Standardized Field Sobriety Tests (SFSTs), and symptoms consistent with Central Nervous System (CNS) depressants, including slurred speech, incoordination, and lethargic behavior. Based on its prevalence and demonstrated impairing effects, bromazolam should be included in the scope of impaired driving testing as long as it continues to be prevalent in the drug supply.