- 學位論文
尿液中愷他命及其代謝物之質譜研究與探討
Simultaneous determination of ketamine and metabolites in urine by mass spectrometry
摘要
有鑑於國內 K 他命濫用情況日趨嚴重，青少年更成為毒品販售的主流，但國內 K 他命之濫用藥物檢驗卻呈現有方法，但不滿意之現狀。由於受到立體障礙之影響，以 GC/MS 進行確認檢驗時，K 他命有衍生效率不穩定之問題，或在真實樣品分析時，競爭不過同時存在之其他胺類藥物之缺點，因此近年來申請通過政府認證之尿液檢驗實驗室，皆大多使用不衍生之分析策略。但不衍生化之 K 他命及其代謝物之分析，其訊號強度較差，對層析管柱要求高，且有層析重疊進而造成內標準品離子干擾之問題。因此本研究嘗試以小型的衍生化試劑(TFAA)，半衍生化試劑(4-CB)與PFBC 衍生化試劑等策略，探討真實樣品中最適當之 K 他命及其代謝物之 GC/MS 分析方法。結果發現 TFAA、4-CB 與 PFBC 衍生後分離效果皆極為良好，但在高濃度安非他命類藥物存在下，TFAA 衍生 K 他命，會出現競爭力不足的問題；4-CB 與 PFBC 衍生化則無競爭力之問題，但PFBC 衍生化有較強的訊號強度。因此，若要進行 K 他命及其代謝物分析，PFBC 衍生化為最佳之選擇，然而，若推廣到同時檢測 K他命類藥物和安非他命類藥物，PFBC 衍生化有一級胺衍生不佳之現象，因此 4-CB 衍生化成為較好之選擇。
並列摘要
Drugs of abuse have become a critical issue in the country and the adolescents are reported to be the main population involved. The identification and quantification of abused substances and their metabolites in urine have been a major task in the forensic drug testing industry. The rapid increase of ketamine (K) abuse worldwide has created a need for a sensitive and reliable detection procedure. This abuse trend has created a need for clinical laboratories to develop more suitable methods for the analysis of K and its metabolites in urine. K and its major metabolite are usually determined with GC-MS. Method of chemical derivatization is the main difference among the GC–MS based methodologies reported for the analysis of ketamine and its major metabolites (norketamine and dehydronorketamine). In principly K can be chemically derivatized with reagents, but popular acylation reagent, HFBA, is not a good choice for derivatization. It is apparent that as a secondary amine, K did not reach an acceptable degree of derivatization reaction. Analytical sensitivity for K after derivatization is low and most researchers have analyzed ketamines without derivatization. In this study, we try to evaluate TFAA、4-CB、PFBC derivatization strategy for ketamine (ketamine: K, norketamine: NK). The results indicated PFBC-derivatives were found to provide the best performance characteristics, but 4-CB derivatization is much better for simultaneous analysis.