Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry.
TL;DR: A validated method for the detection and quantification of naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018), an ingredient of a herbal mixture called "Spice", by means of HPLC-ESI-MS-MS in serum is described.
About: This article is published in Journal of Chromatography B.The article was published on 2010-10-01. It has received 196 citations till now. The article focuses on the topics: Liquid chromatography–mass spectrometry & Detection limit.
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TL;DR: A comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications is presented, showing in vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC.
549 citations
Cites background from "Sensitive and rapid quantification ..."
...Immediate effects included sedation, dry mouth, feeling sick, subjective thought disruption, burning eyes, hot flushes, and tachycardia (Teske et al., 2010)....
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TL;DR: A review of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances is provided in this paper.
Abstract: “K2” and “Spice” drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as “legal highs”. These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate “not for human consumption”, the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications.
437 citations
Cites background or methods from "Sensitive and rapid quantification ..."
...(Hudson et al., 2010b; Teske et al., 2010) as are downstream metabolites of several synthetic cannabinoids (Chimalakonda et al....
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...…and quantifying synthetic cannabinoids used within Spice herbal products, including liquid chromatography tandem mass spectrometry (LC-MS/MS) (Teske et al., 2010) and high mass resolution techniques like matrix-assisted laser desorption/ ionization-time of flight mass spectrometry…...
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...N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript (Hudson et al., 2010b; Teske et al., 2010) as are downstream metabolites of several synthetic cannabinoids (Chimalakonda et al., 2011a, 2011b; Dresen et al., 2010, 2011; ElSohly et al., 2011; Grigoryev et al.,…...
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...For example, after consumption of “Smoke”, “Spice Gold” or other Spice products, some users report sedation while others relate agitation, sickness, hot flushes, burning eyes and xerostomia along with mydriasis and tachycardia (Auwärter et al., 2009; Teske et al., 2010)....
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...Over the past few years, great effort has been given to developing testing strategies capable of identifying and quantifying synthetic cannabinoids used within Spice herbal products, including liquid chromatography tandem mass spectrometry (LC-MS/MS) (Teske et al., 2010) and high mass resolution techniques like matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDI-TOF) (Gottardo et al....
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TL;DR: An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology, and safety.
Abstract: Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC), the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in “head shops” under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as “Spice drugs” or “legal highs”) do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naive individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a “dog chasing its tail” situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.
400 citations
Cites background or methods from "Sensitive and rapid quantification ..."
...…of synthetic cannabinoids in human serum have been developed and validated in accordance with conventional screening protocols based on enzymatic hydrolysis, liquid–liquid extraction, and liquid chromatography/electrospray tandem mass spectrometry analysis (Müller et al., 2010; Teske et al., 2010)....
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...…plants with white or blue water lily (Nymphaea alba or Nymphaea caerulea), Indian Warrior (Pedicularis densiflora), Lion’s Ear (also known as Lion’s Tail or Wild Dagga; L. leonurus), Maconha Brava (Zornia latifolia), and Honeyweed or Siberian Motherwort (Leonurus sibiricus; Teske et al., 2010)....
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TL;DR: Although it remains unclear where and how the actual production of the herbal mixtures takes place, it is evident that producers are purposely risk the health of consumers to skim high profits.
332 citations
TL;DR: The background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures are discussed.
Abstract: Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called “bath salts,” have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as “legal ketamine.” Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as “legal Ecstasy.” These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.
324 citations
References
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TL;DR: Practical, experimental approaches for studying, identifying, and eliminating the effect of matrix on the results of quantitative analyses by HPLC-MS/MS are described and it is demonstrated that, for the investigational drug under study, the matrix effect was clearly observed when ISP interface was utilized but it was absent when the HN interface was employed.
Abstract: In recent years, high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection has been demonstrated to be a powerful technique for the quantitative determination of drugs and metabolites in biological fluids. However, the common and early perception that utilization of HPLC−MS/MS practically guarantees selectivity is being challenged by a number of reported examples of lack of selectivity due to ion suppression or enhancement caused by the sample matrix and interferences from metabolites. In light of these serious method liabilities, questions about how to develop and validate reliable HPLC−MS/MS methods, especially for supporting long-term human pharmacokinetic studies, are being raised. The central issue is what experiments, in addition to the validation data usually provided for the conventional bioanalytical methods, need to be conducted to confirm HPLC−MS/MS assay selectivity and reliability. The current regulatory requirements include the need for the assessment and...
4,543 citations
621 citations
TL;DR: This is the first report of the appearance JWH-073 as a new designer drug and the data and method presented here will facilitate and accelerate the detection of these compounds in complex matrices.
293 citations
Journal Article•
TL;DR: Six novel aminoalkylindole analogs, related structurally to the dual cyclooxygenase inhibitor and nonopioid analgesic pravadoline, were evaluated in the mouse to determine whether their pharmacological profile of activity was similar to that exhibited by delta 9-tetrahydrocannabinol (delta 9-THC).
Abstract: Six novel aminoalkylindole analogs, related structurally to the dual cyclooxygenase inhibitor and nonopioid analgesic pravadoline, were evaluated in the mouse to determine whether their pharmacological profile of activity was similar to that exhibited by delta 9-tetrahydrocannabinol (delta 9-THC). Analog I (C2-H; C3-methoxy-benzoyl) reduced locomotion, but had no other effects (hypothermia, antinociception or ring-immobility) up to 21 mumol/kg. Analogs II and III (C3-naphthoyl; C2-H and C2-methyl, respectively) possessed all properties exhibited by delta 9-THC with ED50 values ranging from 0.68 to 18 mumol/kg. Analog IV (C2-methyl; C3-anthroyl) was devoid of activity. Stereoselectivity was demonstrated by the fact that (+)-WIN-55,212 (one isomer of a semirigid derivative possessing C2-H and C3-naphthoyl substituents) was moderately potent in all tests (ED50 values ranging from 0.25-23 mumol/kg), but (-)-WIN-55,212 was inactive up to 57 mumol/kg. Active aminoalkylindole compounds were generally least effective in the production of hypothermia. Analogs were also evaluated for their ability to produce delta 9-THC-like discriminative stimulus effects in rats. The ED50 for delta 9-THC as a discriminative stimuli for this model was 1.9 mumol/kg. Analog II and III and (+)-WIN-55,212 produced delta 9-THC-like discriminative effects with ED50 values ranging from 0.33 to 4.3 mumol/kg, whereas analogs I, IV and (-)-WIN-55,212 did not. Although reported to be cannabinoid receptor antagonists in vitro, neither analog I, analog IV nor (-)-WIN-55,212 (at 20 mumol/kg) antagonized the in vivo pharmacological effects of delta 9-THC in the mouse or rat.(ABSTRACT TRUNCATED AT 250 WORDS)
282 citations
TL;DR: The morpholinoethyl of WIN 55,212-2 was replaced with carbon chains of varying lengths ranging from a methyl to heptyl group, revealing that high affinity binding to the CB(1) and CB(2) receptors requires an alkyl chain length of at least three carbons with optimum binding to both receptors occurring with a five carbon side chain.
253 citations