Arkansas State Crime Laboratory

Arkansas City, AR, United States

Arkansas State Crime Laboratory

Arkansas City, AR, United States
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Chimalakonda K.C.,University of Arkansas for Medical Sciences | Bratton S.M.,University of Arkansas for Medical Sciences | Brents L.K.,University of Arkansas for Medical Sciences | Moran C.L.,Arkansas State Crime Laboratory | And 6 more authors.
Drug Metabolism and Disposition | Year: 2012

Abuse of synthetic cannabinoids (SCs), such as [1-naphthalenyl-(1-pentyl- 1H-indol-3-yl]-methanone (JWH-018) and [1-(5-fluoropentyl)-1H-indol-3-yl]-1- naphthalenyl-methanone (AM2201), is increasing at an alarming rate. Although very little is known about the metabolism and toxicology of these popular designer drugs, mass spectrometric analysis of human urine specimens after JWH-018 and AM2201 exposure identified monohydroxylated and carboxylated derivatives as major metabolites. The present study extends these initial findings by testing the hypothesis that JWH-018 and its fluorinated counterpart AM2201 are subject to cytochrome P450 (P450)-mediated oxidation, forming potent hydroxylated metabolites that retain significant affinity and activity at the cannabinoid 1 (CB1) receptor. Kinetic analysis using human liver microsomes and recombinant human protein identified CYP2C9 and CYP1A2 as major P450s involved in the oxidation of the JWH-018 and AM2201. In vitro metabolite formation mirrored human urinary metabolic profiles, and each of the primary enzymes exhibited high affinity (Km = 0.81-7.3 μM) and low to high reaction velocities (Vmax = 0.0053-2.7 nmol of product· min-1·nmol protein-1). The contribution of CYP2C19, 2D6, 2E1, and 3A4 in the hepatic metabolic clearance of these synthetic cannabinoids was minimal (fm = <0.2). In vitro studies demonstrated that the primary metabolites produced in humans display high affinity and intrinsic activity at the CB1 receptor, which was attenuated by the CB1 receptor antagonist (6aR,10aR)-3-(1- methanesulfonylamino-4-hexyn-6-yl)-6a,7,10,10a-tetrahydro-6,6, 9-trimethyl-6H-dibenzo[b,d]pyran (O-2050). Results from the present study provide critical, missing data related to potential toxicological properties of "K2" parent compounds and their human metabolites, including mechanism(s) of action at cannabinoid receptors. Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics.

Chimalakonda K.C.,University of Arkansas for Medical Sciences | Bratton S.M.,University of Arkansas for Medical Sciences | Yiew K.H.,University of Arkansas for Medical Sciences | Dineva A.,University of Arkansas for Medical Sciences | And 4 more authors.
Drug Metabolism and Disposition | Year: 2011

K2, a synthetic cannabinoid (SC), is an emerging drug of abuse touted as "legal marijuana" and marketed to young teens and first-time drug users. Symptoms associated with K2 use include extreme agitation, syncope, tachycardia, and visual and auditory hallucinations. One major challenge to clinicians is the lack of clinical, pharmacological, and metabolic information for the detection and characterization of K2 and its metabolites in human samples. Information on the metabolic pathway of SCs is very limited. However, previous reports have shown the metabolites of these compounds are excreted primarily as glucuronic acid conjugates. Based on this information, this study evaluates nine human recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms and human liver and intestinal microsomes for their ability to glucuronidate hydroxylated metabolites of 1-naphthalenyl-1(1- pentyl-1H-indol-3-yl)-methanone (JWH-018) and (1-butyl-1H-indol- 3-yl)-1-naphthalenyl-methanone (JWH-073), the two most common SCs found in K2 products. Conjugates were identified and characterized using liquid chromatography/tandem mass spectrometry, whereas kinetic parameters were quantified using high-performance liquid chromatography-UV-visible methods. UGT1A1, UGT1A3, UGT1A9, UGT1A10, and UGT2B7 were shown to be the major enzymes involved, showing relatively high affinity with K mranging from 12 to 18 μM for some hydroxylated K2s. These UGTs also exhibited a high metabolic capacity for these compounds, which indicates that K2 metabolites may be rapidly glucuronidated and eliminated from the body. Studies of K2 metabolites will help future development and validation of a specific assay for K2 and its metabolites and will allow researchers to fully explore their pharmacological actions. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.

Lapoint J.,New York City Poison Control Center | Lapoint J.,Bellevue Hospital Center | Lapoint J.,New York University | James L.P.,University of Arkansas for Medical Sciences | And 8 more authors.
Clinical Toxicology | Year: 2011

Objective. To report a case of seizures and supraventricular tachycardia (SVT) following confirmed synthetic cannabinoid ingestion. Background. Despite widespread use of legal synthetic cannabinoids, reports of serious toxicity following confirmed use of synthetic cannabinoids are rare. We report severe toxicity including seizures following intentional ingestion of the synthetic cannabinoid JWH-018 and detail confirmation by laboratory analysis. Case Report. A healthy 48 year old man had a generalized seizure within thirty minutes of ingesting an ethanol mixture containing a white powder he purchased from the Internet in an attempt to get high. Seizures recurred and abated with lorazepam. Initial vital signs were: pulse, 106/min; BP, 140/88 mmHg; respirations, 22/min; temperature, 37.7 °C. A noncontrast computed tomography of the brain and EEG were negative, and serum chemistry values were normal. The blood ethanol concentration was 3.8 mg/dL and the CPK 2,649 U/L. Urine drug screening by EMIT was negative for common drugs of abuse, including tetrahydrocannabinol. On hospital day 1, he developed medically refractory SVT. The patient had no further complications and was discharged in his normal state of health 10 days after admission. The original powder was confirmed by gas chromatography mass spectrometry to be JWH-018, and a primary JWH-018 metabolite was detected in the patient's urine (200 nM) using liquid chromatography tandem mass spectrometry. Discussion. Synthetic cannabinoids are legal in many parts of the world and easily obtained over the Internet. Data on human toxicity are limited and real-time confirmatory testing is unavailable to clinicians. The potential for toxicity exists for users mistakenly associating the dose and side effect profiles of synthetic cannabinoids to those of marijuana. Conclusion. Ingestion of JWH-018 can produce seizures and tachyarrhythmias. Clinicians, lawmakers, and the general public need to be aware of the potential for toxicity associated with synthetic cannabinoid use. © 2011 Informa Healthcare USA, Inc.

Pulla S.,University of Arkansas for Medical Sciences | Rusch N.J.,University of Arkansas for Medical Sciences | Moran C.L.,Arkansas State Crime Laboratory | Fantegrossi W.E.,University of Arkansas for Medical Sciences | And 6 more authors.
Analytical Chemistry | Year: 2014

Opioid abuse involving emerging opioid compounds is a growing public health problem, which was highlighted recently by cases of human morbidity and mortality linked to acetyl fentanyl abuse. Unfortunately, the lack of information available on the toxicology and metabolism of acetyl fentanyl precludes its detection in human samples. The following study was conducted to test a new analytical procedure for the simultaneous quantification of acetyl fentanyl and its predicted metabolite, acetyl norfentanyl, in human urine. Metabolic reference standards and deuterium-labeled internal standards were synthesized for use in an assay that coupled solid-phase extraction (SPE) with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The accuracy (% Relative Error <5%) and inter- and intrarun precision (%CV <20%) of this new method resulted in low levels of quantification (∼1 ng/mL). Similar results were obtained using liquid chromatography columns manufactured with phenyl-hexyl and biphenyl stationary phases (r2 > 0.98). Preliminary human liver microsomal and in vivo rodent studies demonstrated that acetyl fentanyl is metabolized by cytochrome P450s to acetyl norfentanyl. Urine samples from rats treated with a toxic dose of acetyl fentanyl contained high concentrations of acetyl fentanyl and acetyl norfentanyl. Further toxicokinetic studies are required to fully elucidate the metabolic pathways responsible for acetyl fentanyl detoxification and excretion. © 2013 American Chemical Society.

Moran C.L.,Arkansas State Crime Laboratory | Chimalakonda K.C.,University of Arkansas for Medical Sciences | Smedley A.L.,Arkansas State Crime Laboratory | Lackey F.D.,Arkansas State Crime Laboratory | And 13 more authors.
Analytical Chemistry | Year: 2011

"K2/SPICE" products are commonly laced with aminoalkylindole synthetic cannabinoids (i.e., JWH-018 and JWH-073) and are touted as "legal" marijuana substitutes. Here we validate a liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for measuring urinary concentrations of JWH-018, JWH-073, and several potential metabolites of each. The analytical procedure has high capacity for sample throughput and does not require solid phase or liquid extraction. Evaluation of human urine specimens collected after the subjects reportedly administered JWH-018 or a mixture of JWH-018 and JWH-073 provides preliminary evidence of clinical utility. Two subjects that consumed JWH-018 primarily excreted glucuronidated conjugates of 5-(3-(1-naphthoyl)-1H-indol-1-yl)-pentanoic acid (>30 ng/mL) and (1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalene-1-yl)-methanone (>50 ng/mL). Interestingly, oxidized metabolites of both JWH-018 and JWH-073 were detected in these specimens, suggesting either metabolic demethylation of JWH-018 to JWH-073 or a nonreported, previous JWH-073 exposure. Metabolic profiles generated from a subject who consumed a mixture of JWH-018 and JWH-073 were similar to profiles generated from subjects who presumably consumed JWH-018 exclusively. Oxidized metabolites of JWH-018 and JWH-073 were of the same pattern, but JWH-018 metabolites were excreted at lower concentrations. These results begin clinically validating the LC-MS/MS assay for detecting and quantifying aminoalkylindole metabolites. Full validation awaits further testing. © 2011 American Chemical Society.

Chimalakonda K.C.,University of Arkansas for Medical Sciences | Moran C.L.,Arkansas State Crime Laboratory | Kennedy P.D.,Cayman Chemical Co. | Endres G.W.,Cayman Chemical Co. | And 9 more authors.
Analytical Chemistry | Year: 2011

The aminoalkylindole agonists JWH-018 and JWH-073 are contained in "K2/SPICE" products sold as "legal marijuana". Previous human metabolic studies have identified (ω)-hydroxyl and (ω)-carboxyl metabolites as biomarkers that are indicative of product use. However, other primary metabolites exhibiting similar chromatographic properties and mass spectra are also excreted in human urine. Analytical standards were used in this study to identify new primary metabolites as (ω-1)-hydroxyl derivatives of JWH-018 and JWH-073. The liquid chromatography tandem mass spectrometry (LC-MS/MS) procedure, coupled with an automated solid-phase extraction procedure incorporating deuterium-labeled internal standards, provides rapid resolution of the (ω)- and (ω-1) metabolites with adequate sensitivity, precision, and accuracy for trace analysis in human urine. Results from four urine specimens collected after individuals reportedly self-administered either JWH-018 or a mixture of JWH-018 and JWH-073 showed the following: (1) all tested metabolites were excreted in high concentrations, (2) (ω)- and (ω-1)-hydroxyl metabolites were exclusively excreted as glucuronic acid conjugates, and (3) ∼5%-80% of the (ω)-carboxyl metabolites was excreted as glucuronic acid conjugates. This is the first report to identify and quantify (ω-1)-hydroxyl metabolites of JWH-018 and JWH-073 and the first to incorporate automated extraction procedures using deuterium-labeled internal standards. Full clinical validation awaits further testing. © 2011 American Chemical Society.

Moran C.L.,Arkansas State Crime Laboratory | Womack M.L.,Arkansas State Crime Laboratory | Prather P.L.,University of Arkansas for Medical Sciences | Fantegrossi W.E.,University of Arkansas for Medical Sciences | And 7 more authors.
Forensic Science International | Year: 2013

New designer drugs such as K2, Spice, and "bath salts" present a formidable challenge for law enforcement and public health officials. The following report summarizes a three-year study of 1320 law enforcement cases involving over 3000 products described as vegetable material, powders, capsules, tablets, blotter paper, or drug paraphernalia. All items were seized in Arkansas from January 2010 through December 2012 and submitted to the Arkansas State Crime Laboratory for analysis. The geographical distribution of these seizures co-localized in areas with higher population, colleges, and universities. Validated forensic testing procedures confirmed the presence of 26 synthetic cannabinoids, 12 designer stimulants, and 5 hallucinogenic-like drugs regulated by the Synthetic Drug Prevention Act of 2012 and other state statutes. Analysis of paraphernalia suggests that these drugs are commonly used concomitantly with other drugs of abuse including marijuana, MDMA, and methamphetamine. Exact designer drug compositions were unpredictable and often formulated with multiple agents, but overall, the synthetic cannabinoids were significantly more prevalent than all the other designer drugs detected. The synthetic cannabinoids JWH-018, AM2201, JWH-122, JWH-210, and XLR11 were most commonly detected in green vegetable material and powder products. The designer stimulants methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy- N-methylcathinone (methylone), and α-methylamino-valerophenone (pentedrone) were commonly detected in tablets, capsules, and powders. Hallucinogenic drugs were rarely detected, but generally found on blotter paper products. Emerging designer drug products remain a significant problem and continued surveillance is needed to protect public health. © 2013 Elsevier Ireland Ltd.

Moreno L.I.,Nuclear DNA Unit | Moreno L.I.,FBI Academy | Tate C.M.,FBI Academy | Knott E.L.,Arkansas State Crime Laboratory | And 6 more authors.
Journal of Forensic Sciences | Year: 2012

The potential application of mRNA for the identification of biological fluids using molecular techniques has been a recent development in forensic serology. Constitutively expressed housekeeping genes can assess the amount of mRNA recovered from a sample, establish its suitability for downstream applications, and provide a reference point to corroborate the identity of the fluid. qPCR was utilized to compare the expression levels of housekeeping genes from forensic-like body fluid stains to establish the most appropriate assessment of human mRNA quantity prior to profiling. Although variability was observed between fluids and individuals, results indicated that beta-2 microglobulin exhibited the highest expression for all body fluids examined and across donors. A one-way analysis of variance was performed for housekeeping gene variability between donors (at the α, 0.05, significance level), and the results indicated significant differences for semen, vaginal secretions, and menstrual blood. 2012 American Academy of Forensic Sciences. Published 2012. This article is a U.S. Government work and is in the public domain in the U.S.A.

Oostdik K.,Promega Corporation | Lenz K.,Promega Corporation | Nye J.,Michigan State Police | Schelling K.,Michigan State Police | And 26 more authors.
Forensic Science International: Genetics | Year: 2014

The original CODIS database based on 13 core STR loci has been overwhelmingly successful for matching suspects with evidence. Yet there remain situations that argue for inclusion of more loci and increased discrimination. The PowerPlex® Fusion System allows simultaneous amplification of the following loci: Amelogenin, D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, DYS391, D8S1179, D12S391, D19S433, FGA, and D22S1045. The comprehensive list of loci amplified by the system generates a profile compatible with databases based on either the expanded CODIS or European Standard Set (ESS) requirements. Developmental validation testing followed SWGDAM guidelines and demonstrated the quality and robustness of the PowerPlex® Fusion System across a number of variables. Consistent and high-quality results were compiled using data from 12 separate forensic and research laboratories. The results verify that the PowerPlex® Fusion System is a robust and reliable STR-typing multiplex suitable for human identification. © 2014 The Authors.

Patton A.L.,Public Health Laboratory | Chimalakonda K.C.,University of Arkansas for Medical Sciences | Moran C.L.,Arkansas State Crime Laboratory | Mccain K.R.,University of Arkansas for Medical Sciences | And 5 more authors.
Journal of Forensic Sciences | Year: 2013

Limited forensic and clinical experience and the lack of confirmatory testing strategies for synthetic cannabinoids (SC) prevent adequate characterization of SC toxicity and the potential impact on public health. A statewide surveillance system identified a fatality involving a 23-year-old man found with a large stab wound to the neck following use of a SC product suspected of containing AM2201. Analytical testing for common SCs, SC metabolites, routine drugs of abuse, and over-the-counter medications was performed on heart blood obtained at autopsy. Additionally, assays were performed on the SC raw material and drug paraphernalia found on the decedent. High concentrations of AM2201 were detected in all samples. AM2201 metabolites were detected in postmortem blood. Other than a trace amount of JWH-073 found in smoke residue, no other substances were detected. Psychiatric complications including self-induced, lethal trauma can occur after the use of SC products. © 2013 American Academy of Forensic Sciences.

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