Journal of analytical toxicology最新文献

In postmortem forensic investigation cases where the bladder is voided or dehydrated prior to autopsy, it is possible to wash the bladder with saline and collect the 'bladder wash' and any residual urine for toxicological analysis. While not conventional, this study aims to determine the use of bladder washes as alternative specimens in postmortem forensic toxicology. Comprehensive drug and alcohol analysis was performed on blood, urine, vitreous humor and bladder wash samples. Control studies consisted of matched bladder wash and urine samples for comparison. Authentic applicability studies were performed on bladder wash samples in cases where only blood or no urine samples were available. Bladder wash testing via the routine urine methodology were shown to have the appropriate sensitivity and specificity to serve as an alternative specimen. Specificity of the applicability studies was further improved when comparisons were corrected by evaluating individual analytes jointly with their related parent drug or metabolites. Individual and corrected sensitivity and specificity rates of above 99% were typically observed in both comparisons against urine and blood paired samples. Following drug analysis of 31 cases in which only a bladder wash was available, 57 detections from 23 different analytes were detected that otherwise would have not been obtained. This study demonstrates that standardized collection of the easily accessible bladder wash for postmortem toxicological analysis serves forensic toxicologists and pathologists with invaluable information where urine or other biological specimens are not available.

Opioids are widely prescribed pain medications that have the potential for misuse and abuse. As part of a routine procedure, our laboratory frequently encounters questions from clients/Medical Review Officers (MROs) regarding opioid hair concentrations in relation to the amount of opioid taken as part of a prescription. In this manuscript, we have analyzed a large number of real-world examples of opioid hair concentrations following self-reported consumption of an opioid prescription regimen. This dataset provides a reference point of opioid hair concentrations after an extensive aqueous wash that likely correspond to consumption of an opioid prescription regimen. Practitioners in the field could use this reference to make decisions on the opioid concentration of a hair sample in relation to a client-provided prescription.

Novel psychoactive substances (NPS) have historically been difficult compounds to analyze in forensic toxicology. The identification, detection and quantitation of these analytes and their metabolites has been difficult due to their rapid emergence, short life span and various potencies. Advancements in analytical instrumentation are fundamental to mitigating these NPS challenges by providing reliable identification and sensitivity. This review discusses the pros and cons of various analytical instruments that have played a pivotal role in NPS analysis. As analytical technology advanced, the ability to analyze for NPS became easier with high resolution mass spectrometry; however, traditional immunoassays are still beneficial for some NPS classes such as benzodiazepines. Over 200 articles from 2010-2023 were reviewed, and 180 were utilized for this review. Journal articles were categorized according to the technology used during analysis: immunoassay, gas chromatography mass spectrometry, liquid chromatography mass spectrometry-low resolution, and liquid chromatography mass spectrometry-high resolution to allow for quick references based on a laboratory's technologies. Journal articles were organized in table format to outline the authors, NPS drug classes, and instrumentation used, among other important information.

The prevalence of mitragynine (kratom) in forensic toxicology casework has steadily increased over time. Readily available and currently legal, mitragynine is widely used for its stimulant and, depending on concentration, sedative effects. Our laboratory analyzed various fluid and tissue specimens from 51 postmortem cases to investigate the distribution of mitragynine and its active metabolite 7-hydroxymitragynine. Central and peripheral blood concentrations were compared, with an average heart blood to femoral blood ratio being 1.37 for mitragynine and 1.08 for 7-hydroxymitragynine. This ratio >1.0 suggests that mitragynine has some propensity toward postmortem redistribution; however, the difference in concentrations of mitragynine and 7-hydroxymitragynine is not statistically significant. Large average mitragynine to 7-hydroxymitragynine ratios of 30.9 in femoral blood and 32.4 in heart blood were observed compared to average ratios of 14.8 in vitreous humor and 16.9 in urine. In addition, the stability of these two compounds was investigated in both matrix and organic solvent. When stored refrigerated (4°C), mitragynine was stable for up to 30 days and 7-hydroxymitragynine was stable for up to 7 days with an analyte loss of <20%. Following 60 days of refrigerated storage, 7-hydroxymitragynine concentrations dropped over 50% from initial concentrations. Methanolic preparations of mitragynine and 7-hydroxymitragynine were stable following 3 months of storage at -20°C.

Dexamphetamine, lisdexamphetamine, and methylphenidate are central stimulant drugs widely used to treat Attention-deficit/hyperactivity disorder (ADHD), but poor adherence may lead to treatment failure and the drugs are also subject to misuse and diversion. Drug analysis in oral fluid may thus be useful for monitoring adherence and misuse. We measured drug concentrations in oral fluid and urine after controlled dosing to investigate detection windows and evaluate the chosen cut-offs. Healthy volunteers ingested single oral doses of 10 mg dexamphetamine (n=11), 30 mg lisdexamphetamine (n=11), or 20 mg methylphenidate (n=10), after which they collected parallel oral fluid and urine samples every 8 hours for 4-6 days. Amphetamine (analytical cut-off, oral fluid: 1.5 ng/mL; urine: 50 ng/mL), methylphenidate (oral fluid: 0.06 ng/mL), and ritalinic acid (urine: 500 ng/mL) were analyzed using fully validated chromatographic methods. The median time from ingestion to the last detection in oral fluid was 67 ± 4.9 (lisdexamphetamine) and 69 ± 8.8 (dexamphetamine) hours for amphetamine and 36 ± 2.5 hours for methylphenidate. This was comparable to urine (77 ± 5.1 hours for lisdexamphetamine, 78 ± 4.5 hours for dexamphetamine, 41 ± 2.4 hours for ritalinic acid). The inter-individual variability in detection times was large, probably in part due to pH-dependent disposition. Using a logistic regression approach, we found similar detection rates as a function of time since intake in urine and oral fluid with the chosen cut-offs, with a high degree of probability for detection at least 24 hours after intake of a low therapeutic dose. This demonstrates the usefulness of oral fluid as a test matrix to assess adherence to ADHD medications, provided the analytical method is sensitive, requiring a cut-off as low as 0.1 ng/mL for methylphenidate. Detection windows similar to those in urine may be achieved for amphetamine and methylphenidate in oral fluid.

Carbon monoxide (CO) is a common gaseous toxin that causes severe poisoning symptoms. Accurate detection of the formation of carboxyhemoglobin (COHb) in the blood is very important for the identification of CO poisoning. In this review, the effects of exogenous toxins, including dichloromethane (DCM), nitrite and hydrogen sulfide, on the determination of COHb by spectrophotometry were summarized by comparing epidemiological data, case studies and analytical methods. The mechanism of the effects of these exogenous poisons on COHb detection is described, and the extent of their influence on the clinical diagnosis and forensic identification of CO poisoning is discussed. We suggest that emergency medicine and forensic science practices need to improve the understanding of these toxins, and optimize clinical diagnosis and evaluation strategies to address the effects of toxins on the determination of COHb.

The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate (GHB-Pal)) in whole blood as a potential biomarker to extend the detection window of GHB use e.g. in drug-facilitated sexual assaults (DFSA). A liquid chromatography-mass spectrometry (LC-MS/MS) method for the quantification of GHB-Pal in whole blood was validated. Whole blood samples were collected from subjects involed in police roadside controls (n=113) and from narcolepsy patients (n=10) after the controlled administration of Xyrem® (sodium oxybate). Both sample collectives were previously tested for GHB using two different methods: ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS). In samples from routine police casework, GHB-Pal was detected in 67 out of 113 analysed GHB-positive samples with a mean concentration of 0.8 ng/mL ± 0.5 ng/mL (standard deviation). Among samples that were tested positive for both compounds, no linear correlation was observed between GHB and GHB-Pal concentrations (r=0.508). In contrast, GHB-Pal was not detected in any of the blood samples analysed from the patients. The absence of GHB and GHB-Pal in the patient cohort may be attributed to the time interval between dose intake and blood collection (approx. 3 and 6 h), during which GHB was eliminated from the body. Furthermore, GHB-Pal was only detectable at a GHB concentration of at least 16 µg/mL, which indicates that endogenous concentrations or low GHB doses may not be sufficient for GHB-Pal formation. Due to missing correlation between both compounds and the lack of GHB-Pal detection several hours after GHB administration, it can be assumed that GHB-Pal in blood is not a suitable biomarker to widen the detection window of GHB.

Ongoing legalization of cannabis for recreational use contributes to increasing numbers not only of incidents of driving under the influence, but within all forensic fields. In addition, newly emerging cannabinoids such as hexahydrocannabinol (HHC) and the increasing use of cannabidiol (CBD) products have to be addressed. The aims of this study were first to extend laboratory analysis capacity for the "established" cannabinoid ∆9-tetrahydrocannabinol (THC) and its metabolites 11-OH-THC and THC-COOH in human plasma/blood, and second to develop analytical procedures concerning HHC and CBD. An LC-MS/MS method based on the available (low-end) instrumentation was used. Samples (250 µL) were prepared by protein precipitation and solid phase extraction. Chromatographic separation was achieved on a reversed-phase C18 column within 15 min. Detection was performed on a 3200 QTRAP instrument (Sciex) in positive multiple reaction monitoring (MRM) mode. Matrix matched six-point calibrations were generated applying deuterated internal standards for all analytes except HHC. The method was fully validated according to GTFCh guidelines. Linear ranges were 0.5-25 µg/L for THC, 11-OH-THC, HHC and CBD, and 2.0-100 µg/L for THC-COOH, respectively. Limits of detection and limits of quantification were 0.5 and 1.0 µg/L (THC, 11-OH-THC, HHC, CBD), and 2.0 and 4.0 µg/L (THC-COOH). Applicability of plasma calibrations to blood samples was demonstrated. Acceptance criteria for intra- and inter-day accuracy, precision, extraction efficiency and matrix effects were met. No interfering signals were detected for more than 60 pharmaceutical compounds. The presented method is sensitive, specific, easy to handle and does not require high-end equipment. Since its implementation and accreditation according to ISO 17025, the method has proven to be fit for purpose not only in DUID cases but also within post-mortem samples. Furthermore, the design of the method allows for an uncomplicated extension to further cannabinoids if required.

The synthetic cathinone (SC) 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP), is structurally correlated to the 3,4-methylenedioxypyrovalerone (MDPV). In recent years, the number of intoxication cases has increased even if little is known about the pharmacokinetics properties. The post-mortem (PM) distribution of MDPHP remains largely unexplored. In these reports, MDPHP levels were quantified in blood, gastric content and urine. This study aimed to describe the MDPHP PM distribution in several specimens, i.e. central and peripheral blood (CB and PB), right and left vitreous humor (rVH and lVH), gastric content (GCo), urine (U) and hair. The samples were collected from a cocaine-addicted 30-year-old man with a PM interval estimated in 3-4 h. Autopsy examination revealed unspecific findings, i.e. cerebral and pulmonary edema. No injection marks were observed. Toxicological analyses were performed using a multi-analytical approach: headspace gas chromatography for blood alcohol content (BAC); gas chromatography-mass spectrometry (GC-MS) for the main drugs of abuse; liquid chromatography-tandem mass spectrometry (LC-MS/MS) for benzodiazepines and new psychoactive substances (NPS). BAC was negative (0.02 g/L). MDPHP concentrations were: 1,639.99 ng/mL, CB; 1,601.90 ng/mL, PB; 12,954.13 ng/mL, U; 3,028.54 ng/mL, GCo; 1,846.45 ng/mL, rVH; 2,568.01 ng/mL, lVH; 152.38 (0.0-1.5 cm) and 451.33 (1.5-3.0 cm) ng/mg, hair. Moreover, hair segments were also positive for 3,4-dimethylmethcathinone (DMMC < limit of quantification: 0.01 ng/mg), α-PHP (0.59 ng/mg, 0.0-1.5 cm; 3.07 ng/mg, 1.5-3.0 cm), cocaine (6.58 ng/mg, 0.0-1.5 cm; 22.82 ng/mg, 1.5-3.0 cm), and benzoylecgonine (1.13 ng/mg, 0.0-1.5 cm; 4.30 ng/mg, 1.5-3.0 cm). MDPHP concentrations were significantly higher than those reported in the literature for fatal cases. For these reasons, the cause of death was probably the consumption of a lethal amount of MDPHP. Because CB and PB were similar, PM redistribution was not relevant.

Since the opioid epidemic was declared in 2017, postmortem fentanyl cases and the need for interpretation of their results have increased. Postmortem redistribution is one of the factors to consider when interpreting cases. There have been several previous studies regarding fentanyl postmortem redistribution; however, these studies either have small sample sizes or were conducted prior to the declaration of the opioid epidemic which may cause conflicting results and not be reflective of current trends. This study includes fentanyl central/peripheral blood ratios from 748 cases from both Harris County, TX and Orange County, TX spanning from January 2009 to June 2022. Because the data set was determined to be non-normally distributed, a Kruskal-Wallis test was used for statistical comparisons. There were statistically significant differences between epidemic cases from the Harris County Institute of Forensic Sciences and the Orange County Crime Laboratory, central/peripheral ratios from pre-epidemic and epidemic years, and in cases where medically-related administration of fentanyl was documented when compared to cases where there was no documentation of licit fentanyl use. Various factors that could impact postmortem redistribution were evaluated (age, gender, polydrug use, etc.) and no clear trend or observation was made from the data. Based on the results of this study, there is still no clear indication as to what caused the increase in central/peripheral ratios, but it may be related to an increase in illicit fentanyl use.