Journal Of Analytical Toxicology[JOURNAL]
Sun
200 papers
Identification of in vivo and in vitro metabolites of fentanyl using UHPLC-Q-Orbitrap-HRMS.
Liu M, Zhao S, Wang BJ … +2 more , Zhou H, Liu Y
J Anal Toxicol · 2025 Apr · PMID 39953785 · Publisher ↗
A comparative analysis of the metabolites and metabolic pathways of fentanyl was conducted in liver microsomes and zebrafish models utilizing ultra-high-performance liquid chromatography coupled with Q Exactive hybrid qu...
A comparative analysis of the metabolites and metabolic pathways of fentanyl was conducted in liver microsomes and zebrafish models utilizing ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A total of 21 metabolites were identified across both liver microsomes and zebrafish models. These included 9 Phase I metabolites, such as N-dealkylated, N-oxidated, and hydroxylated products, and 12 Phase II metabolites, including glucuronidated, methylated, and sulfated products, as well as a series of products derived from conjugation with glutathione (GSH). Notably, the products derived from conjugation with GSH are reported here for the first time. This study provides a comprehensive and in-depth comparative analysis of fentanyl metabolism in liver microsomes and zebrafish, offering a foundation for analyzing and identifying biological samples in cases of fentanyl misuse and fatalities.
Development of a dried blood spot screening test using gas chromatography coupled to high-resolution mass spectrometry: application in authentic postmortem samples.
Dubois-Chabert D, Flament E, Hoizey G … +3 more , Chatenay C, Fanton L, Bottinelli C
J Anal Toxicol · 2025 May · PMID 39953782 · Publisher ↗
This study aims to develop a toxicological screening analysis using gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS) on postmortem dried blood spots (DBSs) and apply it to authentic cases. Twen...
This study aims to develop a toxicological screening analysis using gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS) on postmortem dried blood spots (DBSs) and apply it to authentic cases. Twenty-five microliters of blood was deposited and dried on a paper card. Compounds of interest were desorbed, extracted, and acetylated, then injected into the GC-HRMS. The limits of detection (LOD) and of identification (LOI) were determined for 22 of the compounds that were most frequently detected in postmortem blood samples in the laboratory in 2022. Stability on DBS was studied at three temperatures (-20°C, +4°C, and +20°C) over 15 days. The method was then applied to 102 postmortem blood samples. Results were compared to the two conventional screening methods implemented in the laboratory: liquid chromatography coupled with diode-array detection and mass spectrometry (LC-DAD-MS) and GC-MS. Selectivity was demonstrated by the analysis of 10 negative postmortem blood samples. All LODs were between <10.0 and 20.0 ng/mL. LOIs were within the therapeutic concentration range for each compound or at a value not leading to acute intoxication (narcotics). Overall, compounds remained stable over the 15 days at all test temperatures, except for midazolam and tramadol and its metabolites. A comparison of screenings of 102 postmortem samples resulted in 239 identifications, corresponding to 74 compounds, across 70 positive cases. In 32 cases, no compound was identified. Compounds of 57% and 60%, respectively, were detected by LC-DAD-MS and GC-MS screenings, while DBS-GC-HRMS identified 81%. Application of the method to a hundred authentic cases demonstrated its ability to meet the constraints of low sample volume, sensitivity, and ease of preservation for urgent cases or cases with limited blood availability.
Psychoactive cocktail consumption on Reunion Island: a case report.
Guyon J, Maillot A, Bastard S … +3 more , Weisse F, Daveluy A, Mété D
J Anal Toxicol · 2025 May · PMID 39953779 · Publisher ↗
Reunion Island is a French department located in the southwestern Indian Ocean, with distinct trends in drug use, drug diversion, and intoxication compared with metropolitan France (e.g. the misuse of drugs-clonazepam an...
Reunion Island is a French department located in the southwestern Indian Ocean, with distinct trends in drug use, drug diversion, and intoxication compared with metropolitan France (e.g. the misuse of drugs-clonazepam and trihexyphenidyl-combined with cannabis or cocaine, which is not observed in metropolitan France). The authors report a case of atypical intoxication in a 16-year-old female who consumed cannabis in conjunction with an unusual powdered mixture containing psychotropic substances. The intoxication led to confusion, hallucinations, sinus tachycardia, and hospitalization. A comprehensive high-resolution mass spectrometry and liquid-chromatography mass spectrometry analysis of her plasma, her urine and a powder found in her possession revealed the presence of the same five medicines: citalopram/escitalopram, paroxetine, sertraline, venlafaxine, and trihexyphenidyl. This case underscores the intricate interactions between psychoactive substances that are never prescribed together in clinical settings, along with the issue of diverted prescription drugs like trihexyphenidyl. It also emphasizes the potential circulation and use of crushed mixtures of medication for recreational purpose. Fortunately, powder analysis provided crucial insight to understand the intoxication.
Retrospective fentanyl analysis in the hair of workplace drug testing subjects.
Stowe GN, Paulsen RB, Schaffer MI
J Anal Toxicol · 2025 Apr · PMID 39953778 · Publisher ↗
The powerful opioid analgesic fentanyl has become readily available in the most recent phase of the ongoing opioid crisis. While fentanyl does have important medicinal uses, it is highly prone to misuse and nonmedical us...
The powerful opioid analgesic fentanyl has become readily available in the most recent phase of the ongoing opioid crisis. While fentanyl does have important medicinal uses, it is highly prone to misuse and nonmedical use. In addition, the relative ease of fentanyl synthesis lends it subject to structural modifications by clandestine chemists to produce fentanyl analogs (often termed fentalogs) that are designed to evade detection by law enforcement and forensic toxicologists. Herein, we report fentanyl data as measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS) with extensively washed hair as the matrix in the USA workforce population over the years 2019-24. The limit of detection and limit of quantitation for our method was set at 1.0 pg analyte/mg hair. From our data, we find that ∼94% of samples with concentrations >150 pg fentanyl/mg hair contained measurable norfentanyl metabolite above 1.0 pg/mg hair. In our studied population, only one sample containing the presence of a fentanyl analog was observed in the absence of fentanyl itself. It thus appears that fentanyl analogs are most often found in combination with, or as contaminants of, fentanyl consumed by our study population.
Correction to: Drug detection in oral fluid and urine after single therapeutic doses of dexamphetamine, lisdexamphetamine, and methylphenidate in healthy volunteers.
J Anal Toxicol · 2025 Mar · PMID 39953776 · Full text
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Determination of tramadol and its metabolite O-desmethyltramadol in vitreous humor. Is it helpful in forensic casework?
Vasileiou K, Nikolaou P, Dona A … +4 more , Papadodima S, Athanaselis S, Spiliopoulou C, Papoutsis I
J Anal Toxicol · 2025 Apr · PMID 39948733 · Full text
In recent years, there has been increasing interest on the use of alternative biological materials in forensic toxicology. Vitreous humor is one of them, which, due to the closed cavity it is contained, has a low degree...
In recent years, there has been increasing interest on the use of alternative biological materials in forensic toxicology. Vitreous humor is one of them, which, due to the closed cavity it is contained, has a low degree of contamination and high purity that makes it ideal for use in postmortem specimens. The aim of this study was to investigate the distribution of tramadol and its active metabolite O-desmethyltramadol in vitreous humor and the usefulness of using this alternative biological matrix in tramadol-related forensic cases. For this purpose, a gas chromatography-mass spectrometric method for the determination of the two analytes in blood and vitreous humor samples, which included solid-phase extraction and derivatization using N,O-Bis(trimethylsilyl)trifluoroacetamide with 1% trimethylsilyl chloride, was developed. The method was fully validated according to international guidelines and was applied to blood and vitreous humor samples from 12 forensic cases. Both substances were found to be readily distributed in vitreous humor, since even in cases of very low concentrations of the analytes in blood, their detection was also possible in vitreous humor. In addition, the vitreous humor to blood concentration ratios were calculated for both substances and the mean values were found to be 0.91 for tramadol and 0.94 for O-desmethyltramadol. The results of our study indicate that the information that can be extracted from the analysis of vitreous humor samples is particularly useful during the investigation of tramadol-related cases. Nevertheless, the need for further study of this alternative material to establish therapeutic and toxic limits becomes apparent.
Blood to serum concentration ratios for ethyl glucuronide and ethyl sulfate after five drinking episodes.
Bantle M, Thierauf-Emberger A, Schröck A … +2 more , Weinmann W, Bell LM
J Anal Toxicol · 2025 Apr · PMID 39943798 · Publisher ↗
Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are mostly analyzed in urine; consequently, most kinetic studies are based on urine samples. In forensic cases, however, it may be necessary to determine these alcohol biom...
Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are mostly analyzed in urine; consequently, most kinetic studies are based on urine samples. In forensic cases, however, it may be necessary to determine these alcohol biomarkers in serum, whole blood, or capillary blood. While there are sufficient data on EtG and EtS in serum after alcohol consumption, the amount of data available on whole blood concentrations is small. Therefore, data on corresponding blood-to-serum ratios seem to gain importance. This study provides data on a drinking experiment with 5 drinking episodes, where serum and whole blood samples were taken simultaneously from 11 healthy participants over 10 days. The samples were analyzed for EtG, EtS, and ethanol. EtG and EtS analysis in whole blood and serum were performed by liquid chromatography-tandem mass spectrometry; ethanol was determined by gas chromatography-flame ionization detection and an alcohol dehydrogenase-based method. EtG and EtS reached their maximum concentration 4-7 h after alcohol consumption. For EtG, a mean blood-to-serum ratio of 0.58 with a range from 0.38 to 0.73 was found; for EtS, the mean ratio was 0.81 with a range from 0.61 to 0.92, indicating a predominant distribution in the serum. For both analytes, high correlation coefficients were obtained when plotting concentrations in serum against concentrations in whole blood. Concerning elimination profiles of the individuals, no time or concentration dependence of EtG or EtS blood-to-serum ratios could be deduced. Neither for EtG nor for EtS was a regularity of curve progressions observed in our test specimens.
Validation of a novel LC-MS-MS method for the separation and differentiation of Δ8- and Δ9-tetrahydrocannabinol isomers and their major metabolites in antemortem whole blood.
Mikhaltsevich P
J Anal Toxicol · 2025 Apr · PMID 39924669 · Publisher ↗
The 2018 Farm Bill legalized hemp and defined it as cannabis plant material having not more than 0.3% ∆9-tetrahydrocannabinol (∆9-THC) by dry weight. This has opened the door for the sale of hemp-derived ∆8-tetrahydrocan...
The 2018 Farm Bill legalized hemp and defined it as cannabis plant material having not more than 0.3% ∆9-tetrahydrocannabinol (∆9-THC) by dry weight. This has opened the door for the sale of hemp-derived ∆8-tetrahydrocannabinol (∆8-THC), a psychoactive isomer of ∆9-THC. Hemp has minimal amounts of naturally occurring ∆8-THC; however, the cannabidiol found in hemp can be chemically converted into ∆8-THC. Unfortunately, depending on the method of conversion, the amount of ∆8-THC, ∆9-THC, and other by-products can vary widely. For many laboratories, the emergence of ∆8-THC products resulted in analytical challenges because of the structural similarity of the isomers resulting in coelution. In response, a novel liquid chromatography-tandem mass spectrometry method was developed to separate the two isomers, with an improved limit of detection (LOD) and lower limit of quantification (LLOQ). With this method, clear separation was achieved between ∆9-THC and ∆8-THC and 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH) and 11-nor-9-carboxy-∆8-tetrahydrocannabinol (∆8-THC-COOH) and a partial separation of 11-hydroxy-∆9-tetrahydrocannabinol (∆9-THC-OH) and 11-hydroxy-∆8-tetrahydrocannabinol (∆8-THC-OH). While ∆9-THC-OH and ∆8-THC-OH did not achieve baseline separation, sufficient separation was achieved to confidently identify and differentiate the two compounds. LOD and LLOQ were the same for quantitative compounds. A quantitative range of 0.5-100 ng/mL was achieved for ∆9-THC, ∆8-THC, and ∆9-THC-OH and 2.5-250 ng/mL for ∆9-THC-COOH. Qualitative analysis with an LOD of 0.5 ng/mL was achieved for ∆8-THC-OH and 2.5 ng/mL for ∆8-THC-COOH. To achieve the desired LODs and LLOQs, alternate multiple reaction monitoring transitions were also explored in addition to those utilized in the laboratory's prior method and other published methods. The method was validated following the American National Standards Institute/Academy Standards Board Standard 036, Standard Practices for Method Validation in Forensic Toxicology with minor exceptions, and was proven to be reliable and robust.
Pregabalin concentrations: establishing 'normal' and 'cause for concern' concentration ranges in postmortem blood.
Nahar LK, Paterson S
J Anal Toxicol · 2025 Apr · PMID 39901734 · Publisher ↗
Pregabalin (PGL) is prescribed for the treatment of neuropathic pain, epilepsy, and general anxiety disorder; however, studies have shown that PGL is being misused. It is generally accepted that those who misuse PGL use...
Pregabalin (PGL) is prescribed for the treatment of neuropathic pain, epilepsy, and general anxiety disorder; however, studies have shown that PGL is being misused. It is generally accepted that those who misuse PGL use it in amounts significantly greater than the recommended therapeutic dose. In some instances, such high doses may be well tolerated, and in some instances, the same dose may cause death. Individual variation and postmortem (PM) changes make it extremely challenging for toxicologists to determine if a drug concentration found at PM was contributory to death or not. Unfortunately, meaningful PM data, which can help with interpreting PGL concentrations in femoral-vein blood, are rare. Only one recommendation was found where an author suggested that a PGL concentration of >25 µg/mL in PM blood should be considered as significant; however, in this case series PGL was only screened for in specific cases. To aid interpretation of PGL concentrations, reference data from toxicological analysis conducted on femoral-vein blood only from all manners of death are needed to compile meaningful and unbiased concentration ranges. This study looked at PGL femoral-vein blood concentrations in PM cases from all manners of death over a 2-year period. As it is impossible to define a PM concentration that should be considered toxic/fatal, this study aimed to provide a concentration cut-off where the PGL may be considered a 'normal' incidental finding (unlikely to be the cause of death) or a 'cause for concern' where it may have been taken in excess and caused or contributed to death. This study recommends that a PGL concentration of ≥20 µg/mL in femoral-vein blood should be considered as significant and a 'cause for concern'. Concentrations of ≤19 µg/mL may be considered a 'normal' incidental finding in death, but tolerance and other drug findings need to be considered.
A validated method for capillary phosphatidylethanol 16:0/18:1 quantification with two different 10-µl volumetric absorptive microsample devices in the same setup.
Andreassen TN, Gule M, Havnen H … +2 more , Spigset O, Skråstad RB
J Anal Toxicol · 2025 Apr · PMID 39882943 · Publisher ↗
There is a growing interest for quantification of drugs in capillary blood. Phosphatidylethanol (PEth) is a biomarker for alcohol intake measured in whole blood, thus making it a candidate for capillary sampling. Our lab...
There is a growing interest for quantification of drugs in capillary blood. Phosphatidylethanol (PEth) is a biomarker for alcohol intake measured in whole blood, thus making it a candidate for capillary sampling. Our laboratory has been running a method for PEth quantification in venous blood since 2016, and we aimed to expand this method to also include capillary dried blood spot (DBS) samples. Two 10-µl volumetric absorptive microsampling (VAMS) devices, Capitainer®B Vanadate and Mitra®, were included in the method development and validated. Calibrators and quality controls were spiked during automatic sample extraction without the VAMS devices present, making it possible to extract and analyze both types of VAMS samples in the same setup. With the Mitra device, all pre-established validation criteria were fulfilled in the measuring range of 0.03 to 4.0 µM (21-2812 ng/mL), including method comparison with our venous blood method. Capitainer fulfilled all validation criteria, except for the accuracy of samples with PEth levels ≥ 0.5 µM (≥ 352 ng/mL) (deviation -17.1% to -20.5%). The correlation analysis between Capitainer and the venous blood results showed no constant bias, but an acceptable small proportional mean difference of -7.6%. Overall, the method validation results for both Capitainer and Mitra were considered acceptable. Both devices were found to be suitable for the analyses of PEth.
Toxicological evaluation, postmortem case descriptions, and pharmacological activity of N,N-dimethylpentylone and related analogs.
Fogarty MF, Walton SE, Truver MT … +10 more , Glatfelter GC, Krotulski AJ, Papsun DM, Lamb M, Chronister CW, Goldberger BA, Walther D, Barba K, Baumann MH, Logan BK
J Anal Toxicol · 2025 Mar · PMID 39865839 · Full text
Identification of N,N-dimethylpentylone (DMP) in counterfeit "Ecstasy" and "Molly" tablets poses risk to public health due to its adverse effects. Little information is available regarding the pharmacological activity or...
Identification of N,N-dimethylpentylone (DMP) in counterfeit "Ecstasy" and "Molly" tablets poses risk to public health due to its adverse effects. Little information is available regarding the pharmacological activity or relevant blood or tissue concentrations of DMP, and even less is known about other structurally related beta-keto methylenedioxyamphetamine analogs on recreational drug markets, such as N-propyl butylone. Here, a novel toxicological assay utilizing liquid chromatography-tandem quadrupole mass spectrometry was developed and validated for the quantitation of DMP and five related synthetic cathinones [eutylone, pentylone, N-ethyl pentylone (NEP), N-propyl butylone, and N-cyclohexyl butylone], with chromatographic resolution from isomeric variants and quantitation performed by standard addition. A forensic series of 125 cases is presented for DMP and related analogs, along with pharmacological activity assessments using monoamine transporter and mouse behavioral assays. The blood concentration range for DMP in postmortem forensic cases was 3.3-4600 ng/mL (mean: 320 ± 570 ng/mL, median: 150 ng/mL), whereas pentylone, the primary N-desmethyl metabolite of DMP, was identified in 98% of cases with a concentration range 1.3-710 ng/mL (mean ± SD: 105 ± 120 ng/mL, median: 71 ng/mL). N-Propyl butylone, a newly identified synthetic cathinone, was quantitated in seven cases (mean ± SD: 82 ± 75 ng/mL, median: 50 ng/mL, range: 1.7-200 ng/mL). DMP displayed potent uptake inhibition at the dopamine transporter [half maximal inhibitory concentration (IC50) of 49 nM], with 100-fold weaker potency at the serotonin transporter (IC50 = 4990 nM). DMP was a locomotor stimulant in mice [medium effective dose (ED50) of 3.5 mg/kg] exhibiting potency relatively similar to eutylone, NEP, and pentylone. Our results show that DMP is a psychomotor stimulant associated with adverse clinical outcomes leading to death. Forensic laboratories must continue to update testing methods to capture emerging drugs, with specific emphasis on resolution and identification of isomeric species. Following the scheduling of DMP in early 2024, there could be an anticipated market shift toward a new unregulated synthetic stimulant to replace DMP.
Bladder wash: a proof of concept as an alternative specimen for postmortem toxicology.
Rodda LN, Candela KE, Hart AP … +4 more , Moffatt EG, Farley MC, Pearring S, Scott KS
J Anal Toxicol · 2025 Mar · PMID 39801271 · Publisher ↗
In postmortem forensic investigation cases where the bladder is voided or dehydrated prior to autopsy, it is possible to wash the bladder with saline to collect the "bladder wash" and any residual urine for toxicological...
In postmortem forensic investigation cases where the bladder is voided or dehydrated prior to autopsy, it is possible to wash the bladder with saline to 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 was 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 not have 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.
Beyond the baseline: quantification of two phosphatidylethanol homologues in whole blood by LC-MS-MS and retrospective data analysis from a National Reference Laboratory.
Mathewson NJ, Okoye NC, Nelson HA … +3 more , Pandya V, Moore C, Johnson-Davis KL
J Anal Toxicol · 2025 Mar · PMID 39801266 · Full text
Alcohol is the most abused substance in Western society, resulting in major economic losses and negative health consequences. Therefore, there is a need for a selective and robust detection method for alcohol consumption...
Alcohol is the most abused substance in Western society, resulting in major economic losses and negative health consequences. Therefore, there is a need for a selective and robust detection method for alcohol consumption in various clinical and forensic settings. This study aimed to validate a mass spectrometry method for quantifying phosphatidylethanol (PEth) and perform retrospective data analysis from the patient population of a national reference laboratory. Quantification of PEth in whole blood was accomplished using an LC-MS-MS assay. Isotopically labeled internal standard for the two PEth homologues was added to the whole-blood specimen, followed by protein precipitation with a mixture of acetonitrile and isopropyl alcohol. After centrifugation, an aliquot of the supernatant was buffered with ammonium acetate before LC-MS-MS analysis on an Agilent 6470 triple quadrupole mass spectrometer coupled to an Agilent 1260 Infinity II LC system. This LC-MS-MS assay was validated for clinical use in accordance with Clinical & Laboratory Standards Institute guidelines. The analytical measurement range, 10-2000 ng/mL, was linear with R2 of 0.999. The within-run and total imprecision was < 5% CV for the low (20 ng/mL), medium (200 ng/mL), and high QC (1000 ng/mL). Results from accuracy and method comparison experiments met the bias criteria of ±15%. Retrospective data analysis showed ∼27% of patients had PEth concentrations <20 ng/mL. Males and females had similar positivity rates for PEth and the positivity rate of women of reproductive age (15-44 years old) was 35% in comparison to 25% in women 45-89 years old. This study's LC-MS-MS method showed acceptable analytical performance in quantifying PEth as a sensitive and specific biomarker for evaluating alcohol consumption. Results from this study may provide an opportunity to educate women of reproductive age on drinking during pregnancy and the long-term effects of alcohol use.
Advances in analytical methodologies for detecting novel psychoactive substances: a review.
Krotulski AJ, Mata DC, Smith CR … +4 more , Palmquist-Orlando KB, Modell C, Vikingsson S, Truver MT
J Anal Toxicol · 2025 Mar · PMID 39786399 · Publisher ↗
Novel psychoactive substances (NPSs) have historically been difficult compounds to analyze in forensic toxicology. The identification, detection, and quantitation of these analytes and their metabolites have been difficu...
Novel psychoactive substances (NPSs) have historically been difficult compounds to analyze in forensic toxicology. The identification, detection, and quantitation of these analytes and their metabolites have been difficult due to their rapid emergence, short lifespan, 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 (MS); however, traditional immunoassays are still beneficial for some NPS classes such as benzodiazepines. Over 200 articles from 2010-23 were reviewed, and 180 were utilized for this review. Journal articles were categorized according to the technology used during analysis: immunoassay, gas chromatography-MS, liquid chromatography-MS-low resolution, and liquid chromatography-MS-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.
Postmortem distribution of mitragynine and 7-hydroxymitragynine in 51 cases.
Osawa KA, Johnson RD
J Anal Toxicol · 2025 Feb · PMID 39777518 · Publisher ↗
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...
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.
Opioid hair concentrations using retrospective prescription data from a United States workplace testing population.
Stowe GN, Paulsen RB, Schaffer MI
J Anal Toxicol · 2025 Mar · PMID 39745837 · Publisher ↗
Opioids are widely prescribed pain medications that have the potential for misuse and abuse. As part of a routine procedure, Psychemedics frequently encounters questions from clients/Medical Review Officers regarding opi...
Opioids are widely prescribed pain medications that have the potential for misuse and abuse. As part of a routine procedure, Psychemedics frequently encounters questions from clients/Medical Review Officers regarding opioid hair concentrations in relation to the amount of opioids taken as part of a prescription. In this article, 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 corresponds 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.
Drug detection in oral fluid and urine after single therapeutic doses of dexamphetamine, lisdexamphetamine, and methylphenidate in healthy volunteers.
Helland A, Muller S, Spigset O … +3 more , Krabseth HM, Hansen M, Skråstad RB
J Anal Toxicol · 2025 Feb · PMID 39697138 · Full text
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...
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 cutoffs. 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 h for 4-6 days. Amphetamine (analytical cutoff, 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 h (lisdexamphetamine) and 69 ± 8.8 h (dexamphetamine) for amphetamine and 36 ± 2.5 h for methylphenidate. This was comparable to urine (77 ± 5.1 h for lisdexamphetamine, 78 ± 4.5 h for dexamphetamine, and 41 ± 2.4 h for ritalinic acid). The interindividual 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 cutoffs, with a high degree of probability for detection at least 24 h 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 that the analytical method is sensitive, requiring a cutoff 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.
Effects of dichloromethane, nitrate, and sulfhemoglobin-induced substances on carboxyhemoglobin detection: a comprehensive review.
Wu J, Luan Y, Zhang Q … +2 more , Wang F, Rao Y
J Anal Toxicol · 2025 Mar · PMID 39686842 · Publisher ↗
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....
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 are 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.
Quantification of ∆9-tetrahydrocannabinol, 11-OH-THC, THC-COOH, hexahydrocannabinol, and cannabidiol in human plasma and blood by liquid chromatography-tandem mass spectrometry.
Pavlic M, Innerhofer C, Pitterl F
J Anal Toxicol · 2025 Feb · PMID 39656878 · Full text
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...
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 80 exogenous 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 driving under the influence of drug cases but also within postmortem samples. Furthermore, the design of the method allows for an uncomplicated extension to further cannabinoids if required.
Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake.
Liut J, Madea B, Meißner D … +4 more , Lützen A, Javidi S, Hess C, Krämer M
J Anal Toxicol · 2025 Feb · PMID 39658023 · Publisher ↗
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 w...
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. 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 (approximately 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.
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