Publication: Sentetik Kannabinoid CUMYL-CYBINACA’ nın in vitro metabolizmasının belirlenmesi
Abstract
CÖZET UMYL-CYBINACA, Mayıs 2016’da Adli Tıp Kurumu İstanbul Narkotik Şubesi’nde bitkisel örneklerde tespit edilmiş yeni bir sentetik kannabinoiddir (SK). Yeni SK’ler rutin analizlerde tespit edilemediğinden bu maddelerin tespit edilmesi için analitik metot geliştirilmesi gerekmektedir. Bu çalışma insan karaciğer mikrozomlarında (HLM) maddenin metabolizmasının incelenmesi ve bu sonuçların gerçek idrar örnekleriyle (n=80) teyit edilmesi ile CUMYL-CYBINACA (SGT-78, CUMYL-4CN-BINACA) maddesinin idrardaki hedef metabolitlerinin tanımlanmasını amaçlamaktadır. Bu çalışmada 5 µM CUMYL-CYBINACA HLM’ler ile 3 saat boyunca inkübe edilmiş ve likit kromatografi yüksek rezolüsyonlu kütle spektrometresi (LC-HRMS) ve özel yazılımlar kullanılarak metabolitler tanımlanmıştır. Bu çalışmada monohidroksilasyon, dealkilasyon, oksidatif desiyanasyon (aldehid), alkol ve karboksilik asit oluşumu, glukuronidasyon ve bu reaksiyonların kombinasyonları ile oluşan 18 metabolit tanımlanmıştır. CUMYL-CYBINACA N-bütanoik asit (M16) HLM’de en baskın metabolit olarak tanımlanmıştır. İdrar örneklerinde CUMYL-CYBINACA tespit edilmemiştir; β-glukuronidaz hidrolizinden sonra CUMYL-CYBINACA N-bütanoik asit (M16) idrarda en baskın metabolit olarak tanımlanmıştır. Bu sonuçlara dayanarak M16 (CUMYL-CYBINACA N-bütanoik asit), M8 ve M11(hidroksikümil CUMYL-CYBINACA) metabolitlerini CUMYL-CYBINACA alımının idrarda tespiti için hedef metabolitler olarak önermekteyiz.
CUMYL-CYBINACA is a recently introduced synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine Istanbul Narcotics Department in May 2016 in Turkey. Recently introduced SCs are not detected in routine analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL-CYBINACA (SGT-78, CUMYL-4CN-BINACA) by investigating its metabolism in human liver microsomes (HLMs) and to confirm the results in authentic urine samples (n=80). In this study, 5 µM CUMYL-CYBINACA was incubated with HLMs for up to 3 h, and metabolites were identified using liquid chromatography high-resolution mass spectrometry (LC-HRMS). Eighteen metabolites were identified formed via monohydroxylation, dealkylation, oxidative decyanation (aldehyde), alcohol and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL-CYBINACA N-butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL-CYBINACA was not detected; CUMYL-CYBINACA N-butanoic acid (M16) was major metabolite in urine after β-glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL-CYBINACA N-butanoic acid), M8 and M11 (hydroxylcumyl CUMYL-CYBINACA) as urinary marker metabolites to detect CUMYL-CYBINACA intake.
CUMYL-CYBINACA is a recently introduced synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine Istanbul Narcotics Department in May 2016 in Turkey. Recently introduced SCs are not detected in routine analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL-CYBINACA (SGT-78, CUMYL-4CN-BINACA) by investigating its metabolism in human liver microsomes (HLMs) and to confirm the results in authentic urine samples (n=80). In this study, 5 µM CUMYL-CYBINACA was incubated with HLMs for up to 3 h, and metabolites were identified using liquid chromatography high-resolution mass spectrometry (LC-HRMS). Eighteen metabolites were identified formed via monohydroxylation, dealkylation, oxidative decyanation (aldehyde), alcohol and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL-CYBINACA N-butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL-CYBINACA was not detected; CUMYL-CYBINACA N-butanoic acid (M16) was major metabolite in urine after β-glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL-CYBINACA N-butanoic acid), M8 and M11 (hydroxylcumyl CUMYL-CYBINACA) as urinary marker metabolites to detect CUMYL-CYBINACA intake.