Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry

Scheidweiler, Karl B.; Jarvis, Michael J. Y.; Huestis, Marilyn A.

doi:10.1007/s00216-014-8118-8

Cited by 121 publications

(110 citation statements)

References 34 publications

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“…Currently, A4 is the most convenient target for ADB-CHMINACA intake, as its standard is available for purchase. Remarkably, although it is recommended for synthetic cannabinoids analysis (25,(37)(38)(39)(40)(41), for ADB-CHMINACA identification, it is not necessary to hydrolyze urine samples as no phase II ADB-CHMINACA metabolite was detected.…”

Section: Comparison To Reference Standardsmentioning

confidence: 99%

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

Carlier

Diao

Sempio

et al. 2017

AAPS J

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Abstract.ADB-CHMINACA (MAB-CHMINACA) is a new synthetic cannabinoid with high potency and many reported adverse events and fatalities. The drug is currently scheduled in several countries in Europe and the USA. Analytical methods need to be developed to confirm ADB-CHMINACA intake for clinical and forensic programs. For many synthetic cannabinoids, parent compound is not detectable in biological samples after intake, making the detection of metabolites the only way to prove consumption. Therefore, detection of ADB-CHMINACA metabolites in biological specimens is critical. Since there are currently no published data on ADB-CHMINACA metabolism, we aimed to identify its major metabolites. Cryopreserved human hepatocytes were incubated with 10 μmol/L ADB-CHMINACA for 3 h. Incubations were analyzed with liquid chromatography on a biphenyl column, high resolution tandem mass spectrometry (orbitrap), and metabolite identification software. A reference standard of six commercially available potential metabolites was simultaneously analyzed under the same conditions to allow correct assignment of isomers. We detected ten major metabolites. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, as also observed with structural analogs' metabolism. Minor reactions also occurred at the tert-butyl chain. Only two analytical standards of potential metabolites matched an actual metabolite detected in hepatocyte incubations. We recommend A9 (ADB-CHMINACA hydroxycyclohexylmethyl), A4 (ADB-CHMINACA 4″-hydroxycyclohexyl), and A6 (ADB-CHMINACA hydroxycyclohexylmethyl) as metabolite targets to document ADB-CHMINACA intake in clinical and forensic cases. Additionally, these results will guide analytical standard manufacturers to better provide suitable references for further studies on ADB-CHMINACA metabolism.

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Section: Comparison To Reference Standardsmentioning

confidence: 99%

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

Carlier

Diao

Sempio

et al. 2017

AAPS J

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“…Urine samples were prepared with and without enzymatic hydrolysis as described previously (18,22). Data acquisition and processing were the same as for hepatocyte samples; all four data mining algorithms were utilized and the search was not restricted to only metabolites previously identified in hepatocytes.…”

Section: Analysis Of Authentic Human Urine Specimensmentioning

confidence: 99%

“…To date, all investigated SC are extensively metabolized in humans and are predominantly excreted as metabolites in urine (16)(17)(18), complicating detection as metabolites are initially unknown. Since urine is the most common matrix in clinical, sport doping, or roadside testing, knowledge of human metabolism is essential for developing effective urine testing methods to verify FDU-PB-22 and FUB-PB-22 consumption.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22

Diao

Scheidweiler

Wohlfarth

et al. 2016

AAPS J

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Abstract. In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 μM FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 μM was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after β-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the same metabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after β-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake.

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“…The screening method was difficult to use for the determination of metabolites due to matrix effects. 22 Scheidweiler et al 23 developed and validated a highly useful novel method for 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoids in urine samples utilizing a LC-QTOF method. The hydrolysis and extraction procedures were optimized and analytical figures of merit determined.…”

Section: Pharmacology and Toxicologymentioning

confidence: 99%

How Present Synthetic Cannabinoids Can Help Predict Symptoms in the Future

Mozayani¹

2016

MOJT

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Abbreviations: SCs, synthetic cannabinoids; Δ-9-THC, delta-9-tetrahydracannabinol; UHPLC, ultra high performance liquid chromatography; DAD, photodiode array; MS, mass spectrometry; GC, gas chromatography; DART, direct analysis in real time; TOF, time of flight spectrometry; NMR, nuclear magnetic resonance; ATR, attenuated total resonance; FTIR, fourier transform infrared spectrometry; TIC, total ion chromatogram; LC-MS/MS, liquid chromatography tandem mass spectrometry; CNS, central nervous system; LOD, limit of detection; LOQ, limit of quantitation; ULOL, upper limit of linearity; DUID, driving under the influence of drug; HLM, human liver microsomes; HPM, human pulmonary microsomes; CES 1, carboxylesterase 1 IntroductionSynthetic cannabinoids (SCs) are synthetic compounds sprayed on herbal products and have spread worldwide since 2004. Many of these compounds, more specifically l-valinamides and l-tert-leucinamides, are often characterized as part of the third, fourth and fifth generation of synthetic cannabinoids. There are many street names for herbal like compounds which are sprayed with these compounds, referred to as "Spice" such as Spice Diamond, Spice Gold, Spice Arctic Energy, Magic, Voodoo and Yucatan Fire. Such drugs are easily obtainable via the Internet, in smoke shops, and street markets. To evade law enforcement, these herbal incense products are often labeled "not for human consumption". Despite this, many countries have entered many synthetic cannabinoids to schedule 1. 1,2Initial reports of synthetic cannabinoids (SCs) in Unites States were in November 2008. In December 2008, German forensic laboratories initially identified JWH-018 and cannabicyclohexanol (CP-47,497 C8 homologue). The synthetic cannabinoids are frequently applied on plant material and inhaled. In January 2010, the popularity of these cannabinoids and their associated products appeared to have increased in the United States.3 Numerous SCs have been identified as adulterants, which have been seized by law enforcement. JWH-018, JWH-073, JWH-200, CP-47,497, and CP-47,497 C8 homologues were the first SCs identified as being abused. New generations of synthetic cannabinoids quickly emerged to evade law enforcement. After various laws were passed in the United States, different generations of SCs emerged varying only by slight modifications in structure. Some recent SCs include AB-CHMINACA and AB-PINACA. These substances are commonly marketed under the guise of being a ''legal high'' with a disclaimer of ''not for human consumption''. Law enforcement, public health officials, and clinicians are encountering cases in which there has been abuse of these substances, 4 requiring up to date information of the drug legislation, chemistry of the compounds and their detection, as well as the toxicology to be able to help identify these compounds when they present clinically.After the passage of the Synthetic Drug Abuse Prevent Act of 2012 in the United States, a third and fourth generation of SCs including UR-144, XLR11, and AKB-48 emerged...

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Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry

Cited by 121 publications

References 34 publications

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22

How Present Synthetic Cannabinoids Can Help Predict Symptoms in the Future

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