透過您的圖書館登入
IP:3.88.254.50
  • 期刊

透過同位素標誌技術建立超靈敏之合成卡西酮分析方法

Determination of Synthetic Cathinones With Chemical Isotope Labeling Strategy

摘要


新興影響精神物質(new psychoactive substances, NPS)近年來成長快速,其中合成卡西酮已經成為主要的濫用藥物之一,又因其種類繁多,使分析合成卡西酮變得更加重要也具有挑戰性。目前偵測合成卡西酮的方法主要仰賴液相層析搭配串聯式質譜儀,其偵測極限最佳可達0.1~0.5 ng/mL,亦可同時分析多種合成卡西酮。為求準確定量,同位素內標準品常被用來校正基質效應產生之偏差。然而,並非所有合成卡西酮都能在市面上找到相對應之內標準品,即使可以獲得價格也非常昂貴,使合成卡西酮的準確定量受到阻礙。化學同位素標記法可以提升在逆相層析的滯留效果與偵測靈敏度,丹磺醯肼(dansyl hydrazine)已經被用來標記許多化合物如酮類、固醇類、有羰基或醛基的物質,並可提升偵測靈敏度。合成卡西酮的共同結構具有貝他位置的酮基,適合應用丹磺醯肼衍生以提升偵測靈敏度。此外,藉由同時使用不同穩定同位素之丹磺醯肼(^(12)C與^(13)C),可以合成各個合成卡西酮的同位素內標準品做為絕對定量之用。本研究藉由化學同位素標記法,開發出更高靈敏度且可以同時準確定量31個合成卡西酮的方法。同時,為了評估此方法的應用性,透過大量稀釋尿液來模擬極低濃度環境,如社區汙水系統,並獲得良好結果。此方法預期可應用於汙水系統並監測特定區域的非法濫用物質使用狀況或延長在生物檢體之可偵測期限。

並列摘要


New psychoactive substances (NPS) have grown rapidly in the past decade. Among them, synthetic cathinones had become one of the major abused species, the fast-growing synthetic cathinone market thus poses an analytical challenge. Current methods for detecting synthetic cathinones mostly relied on liquid chromatography coupled to tandem mass spectrometry techniques. For accurate quantification, isotope-labeled internal standards (ISTD) are necessary to counter matrix effect among biological samples. However, commercial ISTD for each compound are expensive and not always available, making absolute quantification more challenged. Chemical isotope labeling (CIL) methods have been developed to improve retention and sensitivity. By employing both light (^(12)C) and heavy version (^(13)C) of dansyl hydrazine (DnsHz), one-on-one internal standards can be successfully synthesized and absolute quantification can be achieved. We optimized several parameters that could influence the derivatization yield including reaction time, reaction solvent and reaction temperature. Multiple reaction monitoring (MRM) transitions for derivatized products at optimal conditions were then optimized. Separation was performed by C18 column after optimizing LC conditions. Method validation was performed by evaluating linearity, accuracy, precision and stability on 31 synthetic cathinones. Our results showed that LODs of 10 species can reach fg/mL level. The values of coefficients of determination (R^2) were all above 0.996. The accuracy and precision of all analytes were in the range of 78-123% and < 18%, respectively. In addition, we employed diluted urine to simulate trace conditions such as sewage system for sewage-based epidemiology (SBE) to test the applicability of this approach. With chemical isotope labeling, we developed a method with better sensitivity and can accurately quantify 31 synthetic cathinones simultaneously. This method is expected to be applied to sewage system and help monitor usage of illicit drugs in a certain area.

參考文獻


Majchrzak M, Celinski R, Kus P, Kowalska T, Sajewicz M: The newest cathinone derivatives as designer drugs: an analytical and toxicological review. Forensic Toxicol 2018;36:33-50. doi:10.1007/s11419-017-0385-6
Pendl E, Pauritsch U, Kollroser M, Schmid MG: Determination of cathinone and cathine in Khat plant material by LC-MS/MS: fresh vs. dried leaves. Forensic Sci Int 2021;319:110658. doi:10.1016/j.forsciint.2020.110658
Lee SF, Hsu J, Tsay WI: The trend of drug abuse in Taiwan during the years 1999 to 2011. J Food Drug Anal 2013;21:390-96. doi:10.1016/j.jfda.2013.09.003
Feng LY, Li JH: New psychoactive substances in Taiwan: challenges and strategies. Curr Opin Psychiatry 2020;33:306-11. doi:10.1097/YCO.0000000000000604
Chou HH, Hsieh CH, Chaou CH, et al.: Synthetic cathinone poisoning from ingestion of drug-laced “instant coffee packets ” in Taiwan. Hum Exp Toxicol 2021;40:1403-12. doi:10.1177/0960327121996043

延伸閱讀