Journal Of Analytical Toxicology[JOURNAL]
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200 papers
In vitro formation of hydroxy metabolites of cocaine and amphetamines in hair after hair product exposure.
Bynum ND, Hart ED, Bollinger K … +5 more , Hayes ED, Flegel RR, Davis LS, Grabenauer M, Winecker RE
J Anal Toxicol · 2026 Apr · PMID 41100347 · Publisher ↗
In hair drug testing for cocaine, the presence of hydroxycocaine metabolites has been suggested as a means of distinguishing between externally contaminated hair and positive hair due to ingestion of drug. However, hydro...
In hair drug testing for cocaine, the presence of hydroxycocaine metabolites has been suggested as a means of distinguishing between externally contaminated hair and positive hair due to ingestion of drug. However, hydroxy compounds can also be produced by the action of certain hair products containing peroxides or other reactive chemicals. In this study, hair samples contaminated with cocaine, benzoylecgonine, methamphetamine, and amphetamine were treated with three hair products: a relaxer containing calcium hydroxide, bleaching colorant containing hydrogen and ammonium hydroxide, and a dye containing hydrogen peroxide to determine the effect of the chemical agents on the drug compounds. Authentic positive hair from people who used drugs were treated with the same hair products. Analysis of the contaminated hair showed that the relaxer removed most of the contaminating drugs with trace production of hydroxy compounds. The peroxide-containing hair products resulted in less reduction in parent drug concentrations and higher concentrations of hydroxy compounds. Analysis of hydroxy to parent compound ratios, specifically for para- and meta-hydroxycocaine, showed that no samples produced ratios at 0.05% or higher-a ratio that has been suggested as indicating drug ingestion. With the authentic drug-positive hair, treatment with the products reduced parent and metabolite concentrations while not affecting hydroxy metabolite to parent ratios.
An in-depth study on Z/E-methoxime isomers in gas chromatography-quadrupole mass spectrometry analysis of C6-keto-opioids in human urine as their methoxime- and acyl-derivatives.
Shoffler KM, Barajas DA, Tomedi MR … +5 more , Hall CL, Reynolds GD, Dinh HT, Castaneto MS, Ke P
J Anal Toxicol · 2026 Apr · PMID 41075178 · Publisher ↗
C6-keto-opioids, such as hydrocodone, hydromorphone, oxycodone, and oxymorphone, are a group of semi-synthetic morphine-like analgesics with extensive applications in clinical settings and high potential for abuse and mi...
C6-keto-opioids, such as hydrocodone, hydromorphone, oxycodone, and oxymorphone, are a group of semi-synthetic morphine-like analgesics with extensive applications in clinical settings and high potential for abuse and misuse. Therefore, they have become targets of workplace forensic urine drug testing for years. Due to the undesired C6-C7 keto-enol tautomerization, the C6 ketone often needs to be deactivated prior to further derivatization for GC-MS analysis. Although it has been over two decades since the method of converting the C6 ketone to its methoxime-derivative was initially reported, little information has been published regarding the resulting Z/E-methoxime-derivative isomers' formation mechanism, stereo-configurations, or relative kinetic or thermodynamic features. Mixed Z/E-methoxime-derivative isomers create a potential peak resolution issue for GC-MS-based C6-keto-opioids identification and quantification, since the two isomers are often difficult to be completely separated by GC and they share common fragmentation pathways. We here provided the first detailed report and qualitative conformational analyses of the Z/E-methoxime-derivative isomers of C6-keto-opioids and their isomerization under the non-aqueous Brønsted-Lowry acidic conditions. By in-depth studying the C6-keto-opioids Z/E-methoxime-derivative isomers, we were able to gain important insights into potential reaction condition optimization with an attempt to reduce the formation of the minor methoxime-derivative isomer, thus, to minimize the potential interferences caused by co-existing of the two isomers and further improve the method's limit of detection and/or limit of quantification. Our report offered valuable information that could facilitate other laboratories using the similar derivatization procedures for GS-MS-based C6-keto-oipoids testing to improve their testing method sensitivity and enhance their analysis product quality.
A highly sensitive headspace gas chromatographic method fully optimized for fast routine determination of carboxyhemoglobin in postmortem blood.
Papoušek R, Gebauerová V, Staňková M … +4 more , Handlos P, Červenková E, Ptáčková D, Borovcová L
J Anal Toxicol · 2026 Apr · PMID 41072931 · Publisher ↗
In some cases, the determination of carboxyhemoglobin (COHb) concentration in postmortem blood using standard spectrophotometric methods, may be either impossible or yield misleading results. In forensic laboratories, th...
In some cases, the determination of carboxyhemoglobin (COHb) concentration in postmortem blood using standard spectrophotometric methods, may be either impossible or yield misleading results. In forensic laboratories, there is an increasing need to analyze COHb saturation in autopsy blood samples, the quality of which is often compromised by various factors. Therefore, a gas chromatographic method has been developed and validated to confirm the results of an established spectrophotometric method and to determine the concentration of COHb in postmortem samples affected by processes such as putrefaction or thermocoagulation. This method is based on automated headspace analysis of a blood sample treated with a solution of potassium hexacyanoferrate and saponin. It employs a combination of two capillary columns for chromatographic separation, followed by a highly sensitive detection system that incorporates a methanizer to convert carbon monoxide (CO) to methane couple to a flame ionization detector. The percentage of COHb concentration is calculated using the ratio of the analyzed blood to that of fully CO-saturated blood. Careful optimization of the method has reduced the sample requirement to 100 mg while maintaining high sensitivity. Additionally, the sample pretreatment process has been simplified to ensure that the method can be easily integrated into the routine operation of a conventional forensic laboratory. The method demonstrates linearity across a concentration range of 0.1% to 100% COHb. The determined values of limit of detection (<0.01% COHb) and limit of quantification (0.1% COHb) reflect excellent sensitivity. Overall, the validation study confirmed the method for its intended purpose. The method is particularly effective in reliably determining COHb content in putrefied and similarly degraded samples. Its robustness has been further validated through the analysis of dozens of real samples over more than 4 years.
Exploring the "poppy seed defense" in oral fluid: detection of opioids following poppy seed consumption.
Midtlyng L, Høiseth G, Rahho R … +1 more , Thaulow CH
J Anal Toxicol · 2026 Apr · PMID 40986378 · Full text
The "poppy seed defense"-a claim that a positive opioid test result is due to ingestion of poppy seeds-is occasionally encountered in forensic toxicology. The matter has been thoroughly investigated in urine but is less...
The "poppy seed defense"-a claim that a positive opioid test result is due to ingestion of poppy seeds-is occasionally encountered in forensic toxicology. The matter has been thoroughly investigated in urine but is less researched in oral fluid. We therefore aimed to perform an experimental study to explore whether consumption of commercially available poppy seeds would lead to detection of opioids in oral fluid. Additionally, we aimed to relate our findings to routine cases. Ten volunteers consumed either five crispbreads containing a small amount of poppy seeds, or 30 g of raw poppy seeds with a low opioid content (3.0 mg/kg morphine and 0.9 mg/kg codeine). Oral fluid samples were collected 0.5 and 2 hours after consumption. Additionally, a urine sample was collected 2 hours after consumption. Following ingestion of raw seeds, morphine was detected (estimated neat oral fluid concentrations 1.4-5.6 ng/mL) in all oral fluid samples 0.5 hours after consumption and in one (2.4 ng/mL) of five oral fluid samples after 2 hours. Codeine was detected (0.8-1.1 ng/mL) in three of five oral fluid samples 0.5 hours after consumption, but in none after 2 hours. Following ingestion of crispbreads, morphine or codeine was not detected in oral fluid, but opioids/-glucuronides were detected in three of five urine samples. When comparing our results with routine cases, we found that 14% of routine cases had morphine concentrations in oral fluid samples lower or similar to those seen after ingestion of raw seeds in our experimental study. In conclusion, we found that consumption of raw seeds led to detection of opioids in oral fluid, but the detection window appeared to be short. Comparison with routine cases indicated that the poppy seed defense may be a challenge when interpreting oral fluid results, particularly when low cut-off levels are applied.
TIAFT President's letter.
Elliott S
J Anal Toxicol · 2025 Jul · PMID 40973162 · Publisher ↗
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Analysis of seven selected cannabinoids in human plasma highlighting matrix and solution stability assessments.
Anderson DJ, Freeman TS, Caldwell KS … +3 more , Hoggard LR, Reilly CA, Rower JE
J Anal Toxicol · 2026 Apr · PMID 40972134 · Full text
Cannabis consumption has and continues to increase dramatically, as does its legalization for recreational and/or medicinal use at the state, but not at the federal level. The increased consumption and legalization have...
Cannabis consumption has and continues to increase dramatically, as does its legalization for recreational and/or medicinal use at the state, but not at the federal level. The increased consumption and legalization have spurred significant cannabis focused research, with particular interest in defining the pharmacokinetic characteristics of this complex natural product. Supporting this research requires a bioanalytical method that accurately and simultaneously quantifies the primary cannabinoids and their metabolites. The objective of this method validation was to meet pre-specified sensitivity targets (0.5 ng/mL for most analytes) from a low sample volume (0.2 mL) and a single extraction approach that could quantify Δ9-tetrahydrocannabinol, cannabidiol, and their metabolites. Moreover, we sought to rigorously characterize the stability of included cannabinoid analytes, both in solution and plasma. The developed assay required optimization of extraction and mobile phase solvents, as well as mass transitions to achieve the selectivity required to meet the desired sensitivity targets. Stability experiments indicated solution stability of no more than 6 months when stored in polypropylene at -30 or -80°C and ∼3 years (34.5 months) of plasma stability when stored in polypropylene at -80°C. The assay was successfully applied to ∼1650 samples without a batch failure. This validated LC-MS/MS assay provides unique information on cannabinoid stability and has been utilized to generate novel data on the pharmacokinetics of cannabis constituents and their metabolites.
Recommendations for toxicological investigation of drug-impaired driving and motor vehicle fatalities-2025 update.
D'Orazio AL, Mohr ALA, Chan-Hosokawa A … +8 more , Harper C, Huestis MA, Kerrigan S, Limoges JF, Miles AK, Scarneo CE, Scott KS, Logan BK
J Anal Toxicol · 2026 Apr · PMID 40972092 · Publisher ↗
This article describes updates to previously published recommendations for drug testing in drug-impaired driving cases. A survey of drug testing practices in driving under the influence of drug and motor vehicle fatality...
This article describes updates to previously published recommendations for drug testing in drug-impaired driving cases. A survey of drug testing practices in driving under the influence of drug and motor vehicle fatality cases was sent to toxicology laboratories across the USA and Canada. Following the compilation of survey data, a virtual consensus meeting was held where forensic science practitioners and the authors reviewed the survey results and conducted a comprehensive review of the 2021 recommendations using a modified Delphi method. Tier I and Tier II screening and confirmation scope and cutoffs were re-evaluated to update the recommendations. Carisoprodol and meprobamate were moved to the Tier II scope from Tier I; gabapentin was promoted to the Tier I scope from Tier II; screening cutoffs were differentiated for immunoassay versus non-immunoassay (e.g. chromatographic) screening for blood and oral fluid; cross-reactivity screening requirements were removed and clarified with specific cutoff values; several cutoffs for screening and confirmation were increased or removed for blood and oral fluid; urine was removed as a recommended matrix for testing in cases involving suspected drug impairment.
Extended urinary opiate detection following ad libitum ingestion of poppy seed pastry.
Reisfield GM, Teitelbaum SA, Mathias KT … +2 more , Jones JT, Lewis B
J Anal Toxicol · 2026 Apr · PMID 40929133 · Publisher ↗
The interpretation of urine drug test results is complicated by the potential for poppy seed ingestion to yield opiate concentrations above standard cutoffs. US federally regulated workplace drug testing programs have ad...
The interpretation of urine drug test results is complicated by the potential for poppy seed ingestion to yield opiate concentrations above standard cutoffs. US federally regulated workplace drug testing programs have adjusted thresholds over time to mitigate this confounder, but the introduction of low cutoffs in clinical settings has reintroduced interpretive challenges. Fifteen adult participants consumed, ad libitum, a portion of a poppy seed kolachi. Urine samples were collected over 5 days and analyzed for codeine and morphine. Detection windows were evaluated across cutoffs ranging from 4000 ng/mL to the assays' limits of detection (8 ng/mL codeine; 10 ng/mL morphine). Opiate detection duration was inversely related to cutoff. At the 4000 ng/mL cutoff, eight participants were codeine-positive at 8 h, with two participants remaining positive at 24 h. At this cutoff, a single participant was morphine-positive through the first 12 h. At 2000 ng/mL, only codeine remained detectable, in a single participant, at 48 h. At 300 ng/mL, seven participants were opiate-positive at 48 h (only codeine, n = 4; only morphine, n = 2; codeine and morphine, n = 1), and four remained positive at 72 h (only codeine, n = 2; only morphine, n = 2). At 50 ng/mL, five participants were opiate-positive at 96 h (only codeine, n = 2; only morphine, n = 2; codeine and morphine, n = 1). Four participants continued to produce detectable opiate concentrations at 108 h (codeine only, n = 1; morphine only, n = 1; codeine and morphine, n = 2). A single ingestion of a commercial poppy seed kolachi produced urinary opiate concentrations exceeding cutoffs from 4000 ng/mL down to the assays' limits of detection, with positivity persisting up to 108 h. These findings underscore the need for cautious interpretation of positive results-especially in settings using low cutoffs-and support the potential utility of adjunctive markers such as thebaine.
Limited added utility of urine ethyl glucuronide compared to blood phosphatidylethanol in a predominantly transplant population.
Snozek CLH, Jannetto PJ, Langman LJ … +1 more , Kinard TN
J Anal Toxicol · 2026 Apr · PMID 40910927 · Publisher ↗
BACKGROUND: Alcohol biomarkers including ethyl glucuronide (EtG) and phosphatidylethanol (PEth) are ordered frequently in clinical and forensic settings including solid organ transplantation. PEth provides a long detecti...
BACKGROUND: Alcohol biomarkers including ethyl glucuronide (EtG) and phosphatidylethanol (PEth) are ordered frequently in clinical and forensic settings including solid organ transplantation. PEth provides a long detection window but can be insensitive to light drinking. In contrast, EtG and ethyl sulfate (EtS) can be elevated after light alcohol consumption and might complement PEth testing. METHODS: Urine EtG/EtS and whole blood PEth results were evaluated from all clinically-ordered testing between 2014 and 2024. PEth and EtG/EtS confirmation were performed by liquid chromatography tandem mass spectrometry at two reference laboratories, using cutoffs: Lab A, PEth 20 ng/ml, EtG and EtS 500 and 250 ng/ml; Lab B, PEth 10 ng/ml, EtG and EtS 250 and 100 ng/ml. Only Lab B performed EtG screening by immunoassay, using a 500 ng/ml cutoff. RESULTS: Phosphatidylethanol was positive in 1269 (15.6%) of 8131 samples, compared to 769 (6.7%) confirmed EtG/EtS positives from 11 555 samples. EtG screening (n = 9668) was positive in 743 (7.7%) samples, of which 30 (4.0%) confirmed negative (false positives); the screen was indeterminate in 267 (2.8%) samples, 66 of which confirmed positive and 172 negative. Of 3132 paired PEth and EtG samples, 2887 (92.2%) were concordant, 224 (7.2%) were PEth-positive, and 21 (0.7%) were EtG-positive. PEth was significantly more sensitive in paired samples (P < .001), even after accounting for potential confounders such as transfusion. Limiting testing to PEth would have correctly identified alcohol consumption in 331 of 373 (88.7%) instances versus EtG/EtS in 149 (39.9%), and reduced charges by >$720 000 USD. DISCUSSION: Phosphatidylethanol outperformed EtG/EtS in detecting alcohol consumption in a predominantly abstinent transplant population. Compared to PEth, EtG/EtS had lower overall positivity and poorer sensitivity in paired samples; additionally, EtG screening demonstrated false positives and indeterminate results. EtG testing provided little added value beyond PEth in this population, and did not warrant the increased cost of performing both tests.
Simultaneous detection and quantification of free phenol and three structural isomers of cresol in human blood using gas chromatography-triple quadrupole mass spectrometry and their medical reference value ranges.
Zhang X, Sun J, Liu J … +10 more , Chen Y, Hong M, Gu J, Zhang S, Rong R, Zhang H, Tian X, Guo T, Wurita A, Chen L
J Anal Toxicol · 2026 Apr · PMID 40910905 · Publisher ↗
Free phenol and cresol isomers in human samples have drawn interest, particularly in the field of forensic toxicology. In this study, a simultaneous analytical method for the detection of unchanged phenol and three struc...
Free phenol and cresol isomers in human samples have drawn interest, particularly in the field of forensic toxicology. In this study, a simultaneous analytical method for the detection of unchanged phenol and three structural isomers of cresol in human blood was developed using gas chromatography-tandem mass spectrometry (GC-MS/MS). This method was applied to authentic human heart and peripheral vein blood samples obtained from a fatal intoxication case involving accidental exposure to liquified phenol containing cresol isomers. In addition, we applied the method to blood samples from 110 healthy individuals. The QuEChERS method was employed for extracting the target compounds, followed by centrifugation. The supernatant of the organic layer was then evaporated by dry nitrogen flow. After the residue was derivatized with 30 μL of N,O-Bis(trimethylsily)trifluoracelamide (BSTFA) BSTFA reagent, the final reconstituted eluate was analyzed by GC-MS/MS. Quantification was performed using the internal standard method for o-cresol and m-cresol, and the standard addition method for phenol and p-cresol. All validation parameters met acceptable criteria. The concentrations of phenol, o-cresol, m-cresol, and p-cresol in heart blood were 335.27, 1.70, 25.27, and 14.21 μg/mL, respectively; in venous blood, the concentrations were 71.43, 1.25, 13.57 and 5.99 μg/mL, respectively. The 95% upper medical reference values (UMRVs) for free phenol and p-cresol in blood from 110 healthy individuals were <0.0865 μg/mL and <0.142 μg/mL, respectively. These data are valuable for evaluating exposure and determining cause of death in forensic investigations.
Expanding fentanyl analog testing to include brain specimens: method validation and homogenate stability assessment.
Behnke G, Skillman B, Palmquist-Orlando K … +2 more , Arndt C, Gray TR
J Anal Toxicol · 2026 Apr · PMID 40910898 · Publisher ↗
The Harris County Institute of Forensic Sciences recently added brain to its fentanyl analog testing method for 14 analogs (fluoroisobutyryl fentanyl, acetyl fentanyl, acryl fentanyl, alfentanil, butyryl fentanyl, carfen...
The Harris County Institute of Forensic Sciences recently added brain to its fentanyl analog testing method for 14 analogs (fluoroisobutyryl fentanyl, acetyl fentanyl, acryl fentanyl, alfentanil, butyryl fentanyl, carfentanil, fentanyl, para-fluorofentanyl, furanyl fentanyl, methoxyacetyl fentanyl, norcarfentanil, norfentanyl, sufentanil, and valeryl fentanyl) and 3 U-series drugs (U-47700, U-48800, and U-49900). Brain is a protected and isolated organ with lower metabolic activity than other tissues, which can assist in interpreting results and preserving parent drug. Limited publications testing brain samples for fentanyl and fentanyl analogs exist and none describe homogenate stability for these analytes. Validation of the solid phase extraction and liquid chromatography tandem mass spectrometry method followed the ASB 036 Standard Practices for Method Validation in Forensic Toxicology and included limit of detection, limit of quantification, calibration model, bias and precision, ionization suppression/enhancement, interferences, carryover, processed sample stability, and dilution integrity. Carfentanil, fentanyl, furanyl fentanyl and methoxyacetyl fentanyl met quantitative bias and precision acceptance criteria in brain. To assess homogenate stability, brain homogenates (both unpreserved and preserved with 1% sodium fluoride) were fortified with 50 ng/mL of analyte, stored at room temperature (∼20°C), refrigerated (2-8°C), or frozen (∼-20°C), and analyzed in triplicate over a 90-day period. Analytes were considered stable if analyte/internal standard response ratio was within ± 20% of Day 0 and chromatographic peaks met qualitative acceptance criteria. Frozen brain homogenates could be stored for up to 90 days and withstood three freeze/thaw cycles for acetyl fentanyl, alfentanil, fentanyl, para-fluorofentanyl, FIBF, methoxyacetyl fentanyl, and norfentanyl. Brain homogenate stability was improved when frozen and was not impacted by the addition of 1% sodium fluoride. The study herein provides insight into the feasibility of testing brain for fentanyl analogs and their stability under various storage conditions, contributing valuable data to the limited literature on brain toxicology testing.
Sodium nitrite intoxications: Quantification of nitrite and nitrate levels in postmortem blood.
Schmitz D, Stach P, Juebner M … +6 more , Scholtis S, Iwersen-Bergmann S, Krüger J, Klima M, Andresen-Streichert H, Lucuta L
J Anal Toxicol · 2026 Apr · PMID 40900657 · Publisher ↗
In recent years, nitrite (salt) overdose has become a method of suicide worldwide. This study presents the development and validation of a high-performance liquid chromatography with diode array detection (HPLC-DAD) meth...
In recent years, nitrite (salt) overdose has become a method of suicide worldwide. This study presents the development and validation of a high-performance liquid chromatography with diode array detection (HPLC-DAD) method for the quantification of nitrite and nitrate in postmortem whole blood. Nitrate measurements were performed after precipitation, filtration, and matrix-clean up. Potassium ferricyanide was used to stabilize nitrite and prevent degradation processes, while the Griess reaction allowed sensitive nitrite quantification. In eleven cases of suspected sodium nitrite intoxication, nitrite concentrations ranged from 1.0 to 529 µg/mL in femoral blood and 1.3-176 µg/mL in heart blood, while nitrate concentrations ranged from 57 to 997 µg/mL and 54-907 µg/mL, respectively. Physiological nitrate concentrations of max. 72 µg/mL were determined in postmortem blood (n = 5), whereas physiological nitrite levels were not detectable (LOD/LOQ: 1 µg/mL). Significant inter-case variability was observed in nitrate and nitrite levels, reflecting the influence of individual postmortem biochemistry, condition, and presumably thanatomicrobial profile and activity, while intra-case discrepancies between femoral and heart blood highlight the importance of analyzing multiple matrices. Nevertheless, an intoxication with sodium nitrite was either concluded if: (i) Nitrite was detected (10/11) or (ii) High nitrate concentrations (above physiological level) were measured (1/11). The interpretation of cases was supported by toxicological data like methemoglobin levels, circumstantial evidence, and morphological findings such as grey skin coloration and chocolate-brown colored blood. The findings enhance the understanding of highly variable nitrate and nitrite dynamics in postmortem toxicology and provide practical insights for forensic investigations, emphasizing the integration of analytical methods, circumstantial, and morphological evidence.
Guanfacine intoxication in a young child presenting with prolonged somnolence and sinus bradycardia: a case report.
Nagasawa S, Inokuchi G, Daikai M … +2 more , Okada H, Iwase H
J Anal Toxicol · 2026 Apr · PMID 40839072 · Publisher ↗
Guanfacine, a medication used to treat attention-deficit hyperactivity disorder (ADHD), activates alpha-2A adrenergic receptors in the brain to reduce symptoms. However, its central alpha-2 agonist activity can cause adv...
Guanfacine, a medication used to treat attention-deficit hyperactivity disorder (ADHD), activates alpha-2A adrenergic receptors in the brain to reduce symptoms. However, its central alpha-2 agonist activity can cause adverse events, such as somnolence, bradycardia, and hypotension. We present the case of a 6-year-old boy (15 kg) with no history of regular medication use who was admitted to the hospital with unexplained prolonged somnolence and bradycardia. Initial evaluation ruled out common causes; however, ingestion of his mother's prescription medication was suspected. Liquid chromatography-quadrupole time-of-flight mass spectrometry confirmed the presence of 6 ng/mL of guanfacine in his serum, which, together with his symptoms, led to a diagnosis of guanfacine intoxication. To our knowledge, this is the first report of guanfacine intoxication in a young child without ADHD with documented serum concentration measurements. This case may help in the recognition and diagnosis of guanfacine toxicity in pediatric patients.
Quantitation of alcohols and acetone in postmortem blood and urine using headspace gas chromatography mass spectrometry.
Edstam M, Sundqvist G, Kronstrand R
J Anal Toxicol · 2026 Apr · PMID 40838999 · Full text
Traditionally, ethanol and related compounds have been analyzed by headspace gas chromatography with flame ionization detection. However, this does not provide structural information, relying solely on retention time for...
Traditionally, ethanol and related compounds have been analyzed by headspace gas chromatography with flame ionization detection. However, this does not provide structural information, relying solely on retention time for identification. With a mass spectrometry (MS) detector, isotope labeled internal standards can be used, eliminating the risk associated with using internal standards like 1-propanol, that can be present in postmortem samples. Furthermore, the use of ion ratios for confirmation of identity eliminates the need for dual injections on columns with different selectivity. In addition, the MS detector provides the ability to include a full scan, which could be helpful in the identification of other volatile unknowns. This prompted the implementation of a headspace gas chromatographic-mass spectrometric method quantifying methanol, ethanol, 2-propanol, 1-propanol, 1-butanol, and acetone while enabling the qualitative detection of a number of other volatiles. A 100 µL sample aliquot was dispensed into a 20 mL headspace vial together with 1000 µL of internal standard solution. Samples were analyzed using an Agilent 7697A headspace sampler coupled to an Agilent Intuvo 9000 gas chromatograph and an Agilent 5977 MS. The developed method was successfully validated and compared to current methodology before being implemented into routine analysis. The introduction of quantitative determination of putrefactive alcohols enables prospective studies of the possible relationship between the formation of ethanol and 1-propanol and 1-butanol and increased the diagnostic power of the method. The simultaneous detection of other volatiles important in postmortem toxicology in all cases increased the scope of routine analysis and the use of MS improved the identification of analytes.
The detection of delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, delta-10-tetrahydrocannabinol, and cannabidiol in hair specimens.
Racines A, Jones J, Lea K … +1 more , Coy D
J Anal Toxicol · 2026 Apr · PMID 40828892 · Full text
Cannabinoid use and misuse has been rising since 2011, and the development of new cannabinoid derivatives, partially due to the passage of the Farm Bill in 2018, and more relaxed legislation, has complicated testing for...
Cannabinoid use and misuse has been rising since 2011, and the development of new cannabinoid derivatives, partially due to the passage of the Farm Bill in 2018, and more relaxed legislation, has complicated testing for this drug class. The impact on child welfare in homes with cannabis substance use remains a concern, so detection of environmental exposure to cannabinoids is hugely beneficial. This article reports a validated confirmation method which detects delta-9-tetrahydrocannabinol (Δ9-THC), delta-8-tetrahydrocannabinol (Δ8-THC), delta-10-tetrahydrocannabinol (Δ10-THC), and cannabidiol (CBD) in environmentally exposed hair specimens via liquid chromatography tandem mass spectrometry (LC-MS-MS) following a supported liquid extraction. From February 2024 to October 2024, 30.5% (n = 1787) of specimens tested positive for at least one analyte. The most common analyte was Δ9-THC (26.8%, n = 1574), followed by Δ8-THC (9.0%, n = 528), CBD (6.1%, n = 359) and Δ10-THC (0.4%, n = 24). While most of the specimens contained multiple analytes, it was found that 21.4% of the positive specimens had a single analyte exposure: 1062 specimens only confirmed for Δ9-THC, 165 specimens only confirmed for Δ8-THC, and 28 specimens only confirmed CBD. The addition of Δ8-THC, Δ10-THC, and CBD to the cannabinoids assay improved the detection of cannabinoids related cases, increasing our total positivity rate by an additional 3.6% (n = 213). The detection of all these analytes is crucial for reliable and accurate detection of cannabinoid environmental exposure.
SIGNIFY™ ER tricyclic antidepressant false positives in diphenhydramine overdose cases.
Nishimura N, Nagasawa S, Inokuchi G … +7 more , Chiba F, Hoshioka Y, Saito N, Yoshida M, Tsuneya S, Yamagishi Y, Iwase H
J Anal Toxicol · 2026 Apr · PMID 40824284 · Publisher ↗
The SIGNIFY™ ER test for diphenhydramine (DPH) overdose yields false-positive results for tricyclic antidepressants (TCA) in multiple cases, complicating the identification of the causative substance of poisoning. We inv...
The SIGNIFY™ ER test for diphenhydramine (DPH) overdose yields false-positive results for tricyclic antidepressants (TCA) in multiple cases, complicating the identification of the causative substance of poisoning. We investigated the causes of TCA false positives in DPH overdose cases. From March 2021 to September 2023, 11 cases of DPH overdose with no concomitant TCA use were identified and categorized into two groups: four with false-positive TCA results (FPG) and seven with negative results (NG) in SIGNIFY™ ER. The blood and urinary DPH concentrations and the urinary concentrations of its three major metabolites (diphenhydramine N-oxide, DPH-NO; N-desmethyl diphenhydramine, DM-DPH; and diphenhydramine N-glucuronide, DPHG) were measured using liquid chromatography quadrupole time-of-flight mass spectrometry, and differences between the groups were examined. Standard substances of DPH, DPH-NO, DM-DPH, DPHG, and mixtures of DPH-NO and DPHG at ratios of 50:50, 25:75, and 75:25 were added to blank urine samples, and TCA was measured using the SIGNIFY™ ER. The concentrations of the substances in the FPG and NG, respectively, were: blood DPH, 0.9-9 and 0.33-49 µg/mL; urinary DPH, 10-110 and 2.3-36 µg/mL; urinary DPH-NO, 110-170 and 0.05-10 µg/mL; urinary DM-DPH, 5.3-47 and 0.13-3.4 µg/mL; and urinary DPHG, 28-370 and 0.24-67 µg/mL. When using spiked urine samples, false positives were obtained for DPH, DPH-NO, DM-DPH, and DPHG at 500, 110, 200, and 70 µg/mL, respectively. In the mixtures of DPH-NO and DPHG, false positives were obtained at all three ratios. TCA false positives in the SIGNIFY™ ER test for DPH overdose cases are suggested to be yielded by DPH-NO and DPHG. For a positive test result without information on TCA use, DPH overdose should be considered.
Xylazine and major urinary metabolites detected in patients positive for fentanyl and xylazine.
Lin Y, Crews BO
J Anal Toxicol · 2026 Apr · PMID 40811054 · Publisher ↗
Xylazine in an anesthetic drug used for the sedation of animals and increasingly appearing as an adulterant in uncontrolled drug supplies, primarily illicit fentanyl. The ability to detect xylazine exposure by urine drug...
Xylazine in an anesthetic drug used for the sedation of animals and increasingly appearing as an adulterant in uncontrolled drug supplies, primarily illicit fentanyl. The ability to detect xylazine exposure by urine drug testing may improve monitoring of this drug trend and our understanding of the effects and risks associated with xylazine exposure. Currently, limited information is available regarding the elimination of xylazine or its metabolites in humans. In this study, we report quantification of xylazine and 4-hydroxy-xylazine (4-OH-x) in hydrolyzed urine specimens collected from 109 patients testing positive for fentanyl and xylazine using liquid chromatography tandem mass spectrometry (LC-MS/MS). 4-hydroxy-xylazine was a minor urinary metabolite in most patients with a median metabolite-to-xylazine (MR) concentration ratio 0.09. Additional urinary metabolites were identified including oxo-xylazine (oxo-x), OH-oxo-xylazine (OH-oxo-x), OH-sulfone-xylazine (OH-sulfone-x), and sulfone-xylazine (sulfone-x), with median MR peak area ratios of < 0.01, 0.60, 0.30, and 1.60, respectively. Sulfone-x signal exceeded that of xylazine in more than 70% of urine specimens. Sulfone-x is not glucuronidated and does not appear to form positional isomers. Additional studies are needed to examine whether detection of xylazine metabolites may improve the sensitivity and/or extend the detection time window for xylazine exposure.
The acute and chronic pharmacokinetics and pharmacodynamics of oral cannabidiol with and without low doses of delta-9-tetrahydrocannabinol.
Wolinsky D, Zamarripa CA, Spindle TR … +11 more , Klausner M, Cone EJ, Winecker RE, Vikingsson S, Flegel RR, Hayes ED, Davis LS, Kuntz D, Bonn-Miller M, Bigelow GE, Vandrey R
J Anal Toxicol · 2026 Apr · PMID 40704705 · Full text
Hemp products [cannabis with ≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)] are federally legal, but few controlled experiments have explored drug test results, pharmacokinetics, or pharmacodynamics. Healthy adults (n = 60) sel...
Hemp products [cannabis with ≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)] are federally legal, but few controlled experiments have explored drug test results, pharmacokinetics, or pharmacodynamics. Healthy adults (n = 60) self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg cannabidiol (CBD) and either 0, 0.5, 1, 2, 2.8, or 3.7 mg Δ9-THC (n = 10 per group). The study included an 8-hour acute dose laboratory session (Phase 1), a 14-day outpatient drug exposure period with twice daily dosing (Phase 2) and a 7-day washout period (Phase 3). Measures including urine, blood, subjective drug effects, and cognitive and psychomotor performance were assessed repeatedly throughout the experiment. At least one participant receiving Δ9-THC doses of 1.0 mg or greater had at least 1 positive urine drug test (Δ9-THC-COOH immunoassay screen ≥50 ng/mL and LC-MS/MS confirmation ≥15 ng/mL) during Phase 1 and the number of positive urine samples increased with Δ9-THC dose. Positive urine drug tests were observed during the Phase 2 outpatient drug exposure period from at least one participant in each dose condition that contained any amount of Δ9-THC. One urine specimen in the CBD only dose condition tested positive during Phase 2. Two positive urine samples were observed after the 1-week washout (Day 21). Blood concentrations of Δ9-THC were very low in all dose conditions, and there were no significant differences between the CBD only dose group and Δ9-THC-containing dose groups on any pharmacodynamic outcome. Individuals subject to drug testing should recognize that hemp products contain detectable amounts of Δ9-THC. Conventional drug testing cannot reliably distinguish between illicit cannabis and legal hemp-derived product use, and a positive urine Δ9-THC test may result from low doses that do not produce intoxication or impairment.
SOFT President's letter.
Heartsill C
J Anal Toxicol · 2025 Oct · PMID 40694608 · Publisher ↗
Abstract loading — click title to view on PubMed.
Etonitazepyne in counterfeit oxycodone tablets-a fatal case report.
Midttun L, Skarshaug LJ, Krabseth HM … +4 more , Gundersen POM, Hansen M, Brekke MB, Frost J
J Anal Toxicol · 2026 Apr · PMID 40694369 · Publisher ↗
Benzimidazole opioids (nitazenes) are novel synthetic opioid receptor agonists that over the last few years have emerged on recreational drug markets, and their abuse has become a concern worldwide. In particular, limite...
Benzimidazole opioids (nitazenes) are novel synthetic opioid receptor agonists that over the last few years have emerged on recreational drug markets, and their abuse has become a concern worldwide. In particular, limited documentation of their pharmacology and toxicology, along with their unpredictable presence in counterfeit medicines mistaken for established brands, pose significant challenges. Herein, we present a case of fatal intoxication with the nitazene etonitazepyne, after intake of tablets appearing like, and thus mistaken as, oxycodone. The assertion of etonitazepyne's implication in the case was delayed by several months, due to lack of information about and access to seized tablets. Eventually, an analytical method using liquid chromatography coupled to a Waters Xevo TQ-S tandem quadrupole mass spectrometer was developed and documented. Using this method, etonitazepyne was confirmed in the tablets and quantified at a concentration of 0.32 ng/mL in both femoral blood and vitreous fluid sampled at autopsy of the deceased. The femoral blood concentration is in the lower range compared to previously published etonitazepyne-related deaths. This case illustrates the challenges with detecting nitazenes and the imminent health risk counterfeit products poses, even for experienced drug users.
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