title: Determination of urinary metabolites of XLR-11 by liquid chromatography-quadrupole time-of-flight mass spectrometry.
abstract: Recently, use of novel synthetic cannabinoids has increased greatly despite worldwide efforts to regulate these drugs. XLR-11 ((1-[5'-fluoropentyl]indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone), a fluorinated synthetic cannabinoid with a tetramethylcyclopropyl moiety, has been frequently abused since 2012. XLR-11 produces a number of metabolites in common with its non-fluorinated parent analogue, UR-144 ((1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone). Therefore, it is essential to develop effective urinary markers to distinguish between these drugs. In this study, we investigated the metabolic profile of authentic human urine specimens from suspected users of XLR-11 using liquid chromatography-quadrupole time-of-flight mass spectrometry. Furthermore, we quantified four potential XLR-11 metabolites by using commercially available reference standards. In vitro metabolism of XLR-11 and UR-144 using human liver microsomes was also investigated to compare patterns of production of hydroxypentyl metabolites. Urine samples were prepared with and without enzymatic hydrolysis, and subjected to solid-phase extraction. We identified 19 metabolites generated by oxidative defluorination, hydroxylation, carboxylation, dehydrogenation, glucuronidation, and combinations of these reactions. Among the identified metabolites, 12 were generated from a cyclopropyl ring-opened XLR-11 degradation product formed during smoking. The XLR-11 metabolite with a hydroxylated 2,4-dimethylpent-1-ene moiety was detected in most specimens after hydrolysis and could be utilized as a specific marker for XLR-11 intake. Quantitative results showed that the concentration ratio of 5- and 4-hydroxypentyl metabolites should also be considered as a useful marker for differentiating between the abuse of XLR-11 and UR-144.
authors.affiliation: National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
authors.forename: Moonhee
authors.initials: M
authors.lastname: Jang
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 426-791, Republic of Korea.
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 426-791, Republic of Korea.
authors.forename: Yu Na
authors.initials: YN
authors.lastname: Park
authors.affiliation: National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
authors.forename: Inhoi
authors.initials: I
authors.lastname: Han
authors.affiliation: National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea.
authors.forename: Seungkyung
authors.initials: S
authors.lastname: Baeck
authors.affiliation: National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea. yangwk@korea.kr.
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 426-791, Republic of Korea. yoohh@hanyang.ac.kr.
authors.forename: Hye Hyun
authors.initials: HH
authors.lastname: Yoo
mesh_terms: D002186:Cannabinoids / Q000378:metabolism / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D002186:Cannabinoids; C585106:XLR-11
keywords: Liquid chromatography–quadrupole time-of-flight mass spectrometry; Synthetic cannabinoid; UR-144; Urinary metabolites; XLR-11