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研究生:柯雅君
研究生(外文):Ya-Chun Ko
論文名稱:以氣相層析質譜儀分析尿液中愷他命代謝物之方法確效
論文名稱(外文):Validation of GC-MS Measurement for Ketamine Metabolites In Urine
指導教授:李宏謨李宏謨引用關係
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學檢驗暨生物技術學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:65
中文關鍵詞:愷他命類代謝物固相萃取氣相層析質譜儀
外文關鍵詞:ketamine metabolitessolid phase extractionGas chromatography-Mass spectrometry
相關次數:
  • 被引用被引用:1
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  • 收藏至我的研究室書目清單書目收藏:0
自95年起愷他命緝獲量已連續五年名列第一,儼然已成為濫用藥物者的新寵。雖然「濫用藥物尿液檢驗作業準則」明定尿液中愷他命之代謝物(愷他命、去甲基愷他命)確認檢驗方法與閾值濃度,但含量較高之代謝物-去氫去甲基愷他命有被檢測之必要性,卻尚未規範於法規中。本研究以尿液中愷他命類代謝物-愷他命、去甲基愷他命及去氫去甲基愷他命為待測物,調整適合層析出愷他命類代謝物之升溫條件,並比較三種不同固相萃取管柱對愷他命類代謝物萃取表現,將固相萃取技術及氣相層析質譜儀分析條件最佳化、正確定量其濃度,並使用經液相層析電噴灑串聯質譜儀檢出愷他命與去甲基愷他命成分之尿液檢體,檢測其愷他命類代謝物之表現情形。結果顯示本分析方法操作簡單、快速、靈敏、穩定,對三種待測物能提供理想的檢量線線性(濃度範圍40至2000 ng/mL,各待測物之r2 皆大於0.990)、敏感度(各待測物之最低可定量濃度皆可至15 ng/mL)、準確度(93.4-101.1%)及精密度 (RSD<9.5%),本方法應可應用於濫用藥物尿液檢驗實務工作。

Since 2006, the total amount of apprehended ketamine happened to be the highest one among all drugs for consecutive five years. It appears that ketamine has become the new favorite of the drug abusing population. Although there are clearly defined standard testing methods for some ketamine metabolites (including ketamine itself and norketamine) in urine samples listed in the “Regulations Governing Drug Abuse Urine Testing Operations” along with their relevant threshold concentrations, another metabolite with even higher content, i.e. dehydronorketamine, which has the necessity to be detected and measured, is not yet included and standardized in the regulation. In this study, we attempt to use three different kinds of novel solid phase extraction cartridges and optimize their analysis conditions of the Gas chromatography-Mass spectrometry during the process to minimize the background noise and maximize the extraction effectiveness for ketamine, norketamine, as well as dehydronorketamine present in the urine sample. To employ urine samples containing ketamine and norketamine had detected by LC-ESI-MS-MS would The results showed that this analytical approach is simple, rapid and reliable, and able to achieve an ideal linearity (r2>0.999 over the concentration range of 40 to 2000 ng/mL), sensitivity (limits of quantification is 15 ng/mL, respectively), accuracy (93.4-101.1%), and precision (RSD<9.5%) for all target components analyzed. This method may be used to detect drugs in urine samples on a regular basis.

Abstract i
中文摘要 ii
目錄 iii
表次 v
圖次 vi
縮寫表 vii
壹、緒論 1
貳、研究動機 4
叁、研究材料與方法 7
一、儀器設備(Instruments) 7
二、材料與試劑(Materials and reagents) 7
三、尿液檢體前處理方法(Urine sample preparation) 9
四、氣相層析質譜儀分析方法(GC-MS analysis) 11
五、統計軟體(Statistics software) 12
肆、實驗結果 13
一、調整升溫條件對於分析上的影響(The effect of GC-MS analysis through temperature program) 13
二、觀察三種固相萃取管柱對於愷他命類代謝物之萃取表現(The express for K, NK and DHNK of three solid phase extraction columns) 14
三、方法確效(Method validation) 15
四、真實尿液檢體之分析(Analysis of urine samples) 18
伍、討論 20
陸、參考文獻 27
Table 1 The change of total running time through rising temperature rate in the 2nd stage. 35
Table 2 The concentration of quality control samples through rising temperature rate in the 3rd stage. 35
Table 3 To compare the detectable expression in three different extraction columns. 36
Table 4 The accuracy and precision of SPEC??・DAU column and Strata C18-E column. 37
Table 5 The recovery of SPEC??・DAU column and Strata C18-E column. 38
Table 6 The concentration of four kinds urine spiked with 30 ng/mL K, NK, and DHNK for specificity. 39
Table 7 The LOD and LOQ value of K, NK and DHNK analyzed by GC–MS. 40
Table 8 The result of K, NK, and DHNK in 114 positive urine samples. 41
Table 9 The performance of GC-MS vs. LC-ESI-MS-MS in 164 urine samples. 45
Figure 1 Total ion chromatogram showed in the different temperature program. 46
Figure 2 Total ion chromatogram through three columns in urine extraction process. 47
Figure 3 Extracted ion chromatogram through three columns in urine extraction process. 48
Figure 4 The calibration curve and linear correlation of K, NK and DHNK. 49
Figure 5 Total ion chromatogram of four kinds urine spiked with 30 ng/mL K, NK, and DHNK for specificity. 50
Figure 6 The linear correlation of K by GC-MS and LC-ESI-MS-MS. 51
Figure 7 The linear correlation of NK by GC-MS and LC-ESI-MS-MS. 52
Figure 8 The concentration distribution chart of K, NK, and DHNK in positive urine samples. 53



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