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研究生:葉雅玲
研究生(外文):Ya-Ling Yeh
論文名稱:唾液與尿液中安非他命類藥物等量閾值之評估
論文名稱(外文):Evaluation of equivalent cutoff values for amphetamines in oral fluid and urine
指導教授:王勝盟王勝盟引用關係
指導教授(外文):Sheng-Meng Wang
學位類別:碩士
校院名稱:中央警察大學
系所名稱:鑑識科學研究所
學門:軍警國防安全學門
學類:警政學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:152
中文關鍵詞:毒駕唾液快篩套組液相層析四極桿柱飛行時間質譜儀等量閾值安非他命
外文關鍵詞:Driving under the influence of drugsDrug oral on-site testingLC-Q-TOFEquivalent cutoff valueAmphetamines
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刑法185-3規定關於毒駕和不能安全駕駛之不確定法律概念並不容易執行,由於唾液較血液侵入性小且相對於尿液可避免摻假,在國外已有許多利用唾液作為現場快速篩檢之套組。目前在台灣僅訂定尿液中相關藥毒物之閾值門檻,須建立唾液相應之等量閾值。
本研究以GC/MS及LC-Q-TOF共分析165組警方路檢攔查疑似吸食安非他命類藥物駕駛之尿液及唾液,檢測方法經過方法驗證後,實際檢體檢測結果去除超過線性範圍,以Box and whisker方法去除離群值後,以OF/U之平均數、OF/U之中位數、唾液與尿液線性迴歸及Prevalence regression進行統計分析,以Prevalence regression和二次迴歸線具有最佳之準確度得到唾液中安非他命等量閾值為44.6ng/mL而甲基安非他命等量閾值為51.8ng/mL。
本研究以50ng/mL作為唾液快篩套組之閾值,評估吸水棉中安非他命回收率為75.3% 而甲基安非他命為84.2%,部分類似結構之藥物會產生偽陽性之結果,實際評估快篩套組之表現其準確度於甲基安非他命為76.7%。研究希冀評估藥物於唾液及尿液之相關性,訂定合理檢測閾值,提供開發唾液毒品快篩套組相應的檢驗依據,並評估快篩套組以供未來執法單位實際執行與應用。
The 185-3 of Criminal Law about the driving under the influence of drugs (DRUID) and the uncertainty concept of unable to driving is not easy to implement. Because of non-invasive alternative to blood and less substitute alternative to urine, there already have many drug oral on-site testing devices conducting in foreign countries. Currently in Taiwan, drug cutoff values only ruled in urine and required to establish equivalent cutoff values in oral fluid.
This study used GC/MS and LC-Q-TOF to analyze a total 165 paired samples of amphetamines of urine and oral fluid collected from the DRUID drivers. Analytical methods have been validated. After deleted the data below the dynamic range and conducted Box and Whisker method to eliminate the outliers, the analytical results of real samples were analyzed with the mean of OF/U, the median of OF/U, the Linear regression curves between urine and oral fluid and Prevalence regression. Quadratic equation of Prevalence regression for amphetamine (AP) and methamphetamine (MA) with the best accuracy obtained equivalent cutoff values in oral fluid of AP is 44.6ng/mL and of MA is 51.8ng/mL.
50ng/mL was settled as the cutoff value of drug oral on-site testing device. The recovery of collection device of AP is 75.3% and of MA is 84.2% and some adulteration substances with similar structure would cause false positive results. Besides, the accuracy of on-site testing device of MA is 76.7%. This study aims to evaluate the correlations of drugs in oral fluid and in urine and set reasonable cutoff values of drugs in oral fluid. The cutoff values offer the drug on-site testing device a corresponding standard. Besides, evaluate the performance of the testing device in order to provide law enforcement agency to implement the device in real and apply in the future.
謝誌 I
摘要 II
ABSTRACT III
TABLE OF CONTENTS V
LIST OF FIGURES IX
LIST OF TABLES XII
LIST OF APPENDIXS XV
CHAPTER 1: INTRODUCTION 1
1.1 RESEARCH MOTIVATION 1
1.2 SPECIFIC OBJECTIVE 3
CHAPTER 2: LITERATURE REVIEW 5
2.1 LIQUID CHROMATOGRAPHY QUADRUPOLE TIME-OF-FLIGHT MASS SPECTROMETRY 5
2.2 DRUG TESTING 7
2.2.1 Drug oral testing 7
2.2.2 Drug Cutoff values in Taiwan and abroad 10
2.3 TOXICITY OF AMPHETAMINES 11
2.3.1 Pharmacokinetics of amphetamines 11
2.3.2 Metabolism of amphetamines 12
2.3.3 Amphetamines and driving 14
2.4 ESTIMATION OF EQUIVALENT CUTOFF VALUES IN URINE AND ORAL FLUID 16
2.4.1 Predicting saliva/plasma concentrations 17
2.4.2 Predicting concentrations in blood and in oral fluid 19
2.4.3 Predicting concentrations in urine and in oral fluid 20
2.5 VALIDATION OF ON-SITE TESTING DEVICE 21
2.5.1 Recovery of collection device 21
2.5.2 Adulteration and interfering substances about amphetamines 22
2.5.3 The capability of on-site testing device 23
CHAPTER 3: METHODOLOGY 24
3.1 REAGENTS 24
3.2 ROADSIDE SAMPLES 24
3.3 ON-SITE TESTING DEVICE 25
3.4 ANALYTICAL METHOD 26
3.4.1 Sample pretreatment procedure 26
3.4.2 LC-Q-TOF condition 28
3.4.3 GC-MS condition 30
3.4.4 Analytical method 30
3.5 VALIDATION OF THE ANALYTICAL METHOD 31
3.5.1 Validation methodology 31
3.5.2 Dynamic range 32
3.5.3 Extraction recovery 34
3.5.4 Within-day and between-day precision and accuracy 34
3.5.5 Matrix effect 35
3.6 ESTIMATION OF EQUIVALENT CUTOFF VALUES IN URINE AND ORAL FLUID 36
3.6.1 Box and whisker plot 36
3.6.2 Pearson Product-Moment Correlation Coefficient 37
3.6.3 Methods for estimation of equivalent cutoff values 39
3.6.4 Validation studies for determining the accuracy and precision 40
3.6.5 Cohen’s Kappa value 40
3.7 VALIDATION OF ON-SITE TESTING DEVICE 41
3.7.1 Recovery of collection device 42
3.7.2 Stability and accuracy of on-site testing device 43
3.7.3 Adulteration and interfering substances about amphetamines 43
3.7.4 The capability of on-site testing device 44
CHAPTER 4: RESULTS AND DISCUSSIONS 46
4.1 CHROMATOGRAMS AND MASS SPECTRUMS 46
4.1.1 LC-Q-TOF 46
4.1.2 GC-MS 53
4.2 VALIDATION OF THE ANALYTICAL METHOD 56
4.2.1 Performance characteristics of LC-Q-TOF methods 56
4.2.2 Performance characteristics of GC–MS methods 61
4.3 ESTIMATION OF EQUIVALENT CUTOFF VALUES IN URINE AND ORAL FLUID 64
4.3.1 Real sample analysis 64
4.3.2 Outliers of oral fluid/ urine 65
4.3.3 Correlations of AP and MA between urine and oral fluid 68
4.3.4 Estimation of equivalent cutoff values 69
4.3.5 Validation studies for determining the accuracy 76
4.4 VALIDATION OF ON-SITE TESTING DEVICE 81
4.4.1 Recovery of collection device 81
4.4.2 Stability and accuracy of on-site testing device 86
4.4.3 Adulteration and interfering substances about amphetamines 88
4.4.4The capability of on-site testing device 92
CHAPTER 5: CONCLUSIONS 107
REFERENCE 110
APPENDIXS 121
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