İdrarda UR-144 ve metabolitlerinin LC-MS/MS ile tayinleri
Loading...
Files
Date
2016
Authors
Karaoğlu, Ergün
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Esrarın yan etkilerini azaltarak tedavi edici etkisini geliştirmek üzere sentezlenen sentetik kannabinoidler son yıllarda esrara alternatif olarak kullanılmakta ve suistimali tehlikeli boyutlara ulaşmıştır. Endokannabinoid reseptörlere tetrahidrokannabinol (THC)'e benzer etki gösteren fakat farklı kimyasal yapıdaki bu maddeler, ciddi yan etkilere hatta ölümlere neden olabilmektedirler. Sentetik kannabinoidlerin bitkisel materyaller üzerine spreylenmesiyle hazırlanan karışımlar "doğal" ve "yasal" kandırmacasıyla internet üzerinden kolaylıkla satılmakta ve popülariteleri gün geçtikçe artmaktadır. Maddelerin farmakolojisi, toksik etkileri ve tayiniyle ilgili yapılan çalışmalar oldukça sınırlıdır. "Tütsü" gibi isimlerle adlandırılan Spice, Yucatan Fire, Smoke, Sence, Skunk ve Space gibi ticari isimlerle piyasaya sürülen bu maddeler esrardan daha güçlü bir etki oluşturmaktadır. Buna ek olarak yasal kapsama alınmadığı için rahatlıkla ticareti yapılabilmektedir. Artan popülaritesi ve olası hasar potansiyeli nedeniyle "spice" Türkiye'de 2011 yılında yasa kapsamına alınması nedeniyle bileşenlerinin analizine adli toksikolojide ihtiyaç duyulmuş ve tayini gerekli hale gelmiştir. UR-144, UR-144 N-pentanoik asit ve UR-144 N-(5-hidroksipentil) maddelerinin katı faz ekstraksiyonu yapılarak LC-MS/MS analizi ile idrarda tayini ve miktar belirlenmesi amacıyla spesifik ve güvenilir bir metot geliştirilmiştir. Metodun validasyonu doğrusallık (0,1 – 100 ng/mL), seçicilik, gün içi ve günler arası doğruluk ve kesinlik (CV < %15), geri kazanım (% 81-99), gözlenebilme sınırı (LOD) (0,05-0,09 ng/mL), ve gözlenebilme miktarı (LOQ) (0,17-0,31 ng/mL) parametreleri dikkate alınarak yapılmıştır. Ayrıca matriks etkisi, kararlılık ve işlem etkileri de incelenmiştir.
Synthetic cannabinoids are synthesized to improve the therapeutic effect of marijuana by reducing the adverse effects of it but cannabis are now being used as alternative of marijuana and its widespreadening has reached dangerous proportions abusively. The endocannabinoid receptors for tetrahydrocannabinol (THC) showing similar effects to these substances but with different chemical structures, they cause serious side effects even death. It is increasingly getting popular and available on internet to reach Synthetic cannabinoids which prepared as liquid spray and applied over mixtured various plant materials under mask of "natural" and "legal" trade labels in the market day by day. Unfortunatelly, pharmacologic, toxic effects and determination of cannobinoid substances related studies are very limited. Trading traffic of those substances in the market held by different names such "Incense, Spice, Yucatan Fire, Smoke, Sence, Skunk" and these substances have more effective than marijuana. Additionaly legal gaps and abstractness of legal regulations provides easiness on trading of that substances in the market. It became required to analyze and identificate for forensic toxicology when a legal legislation made in 2011 which aims to prevent the dangerously increasing popularity and damage potential of "spice" in Turkey. A specific and reliable method has been developed for the detection and quantification of UR-144, UR-144 N-pentanoic acid and UR-144 N- (5-hydroxypentyl) in urine using solid-phase extraction by LC–MS/MS analysis. The method has been validated in terms of linearity (0,1 – 100 ng/mL), selectivity, intra-assay and inter-assay accuracy and precision (CV < 15%), recovery (81-99%), limits of detection (LOD) (0,05-0,09 ng/mL), and quantification (LOQ) (0,17- 0,31 ng/mL). Matrix effects, stability, and process efficiency were also assessed.
Synthetic cannabinoids are synthesized to improve the therapeutic effect of marijuana by reducing the adverse effects of it but cannabis are now being used as alternative of marijuana and its widespreadening has reached dangerous proportions abusively. The endocannabinoid receptors for tetrahydrocannabinol (THC) showing similar effects to these substances but with different chemical structures, they cause serious side effects even death. It is increasingly getting popular and available on internet to reach Synthetic cannabinoids which prepared as liquid spray and applied over mixtured various plant materials under mask of "natural" and "legal" trade labels in the market day by day. Unfortunatelly, pharmacologic, toxic effects and determination of cannobinoid substances related studies are very limited. Trading traffic of those substances in the market held by different names such "Incense, Spice, Yucatan Fire, Smoke, Sence, Skunk" and these substances have more effective than marijuana. Additionaly legal gaps and abstractness of legal regulations provides easiness on trading of that substances in the market. It became required to analyze and identificate for forensic toxicology when a legal legislation made in 2011 which aims to prevent the dangerously increasing popularity and damage potential of "spice" in Turkey. A specific and reliable method has been developed for the detection and quantification of UR-144, UR-144 N-pentanoic acid and UR-144 N- (5-hydroxypentyl) in urine using solid-phase extraction by LC–MS/MS analysis. The method has been validated in terms of linearity (0,1 – 100 ng/mL), selectivity, intra-assay and inter-assay accuracy and precision (CV < 15%), recovery (81-99%), limits of detection (LOD) (0,05-0,09 ng/mL), and quantification (LOQ) (0,17- 0,31 ng/mL). Matrix effects, stability, and process efficiency were also assessed.
Description
Keywords
Sentetik kannabinoid, LC-MS/MS, UR-144, Metabolit, İdrar, Synthetic cannabinoid, Metabolites, Urine
Citation
Karaoğlu, E. (2016). İdrarda UR-144 ve metabolitlerinin LC-MS/MS ile tayinleri. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Fen Bilimleri Enstitüsü.