生物檢體中管制藥品之氣相層析質譜研究｜國立清華大學博碩士論文庫

簡易檢索 / 詳目顯示

回結果列表

研究生：	周素蓮 Su-Lien Chou
論文名稱：	生物檢體中管制藥品之氣相層析質譜研究 Gas Chromatography-Mass Spectrometry Analyses of Controlled Drugs and Their Metabolites in Biological Specimens
指導教授：	楊末雄 Mo-Hsiung Yang 凌永健 Yong-Chien Ling
口試委員:
學位類別：	博士 Doctor
系所名稱：	原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences
論文出版年：	2008
畢業學年度：	96
語文別：	英文
論文頁數：	149
中文關鍵詞：	鴉片類、安非他命類、快樂丸、二亞甲基雙氧安非他命、大麻、K他命、氣相層析質譜儀、管制藥品、生物檢體
外文關鍵詞：	opiates, amphetamines, MDMA, MDA, ketamine, marijuana, GC-MS, controlled drugs, Metabolites
相關次數：	點閱：1 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

摘要
本論文針對目前管制藥品中最被嚴重濫用之鴉片類、安非他命類、快樂丸(3,4 methylenedioxymethamphetamine, MDMA )、二亞甲基雙氧安非他命（MDA）、K他命( ketamine )及大麻等濫用藥物，利用氣相層析質譜儀(GC-MS)檢測尿液、頭髮等生物檢體中及可能殘留於現場空氣中之管制藥品跡證，以評估其檢出情形或確認是否有上述藥品之殘存。
論文共分五部分。第一部份：主要利用液相-液相萃取（LLE）方法將尿液檢體中K他命（KT）及其代謝物正K他命（NK）萃取後，再以五氟苯醯氯(pentafluorobenzoyl chloride, PFBC)衍生，以分別進行GC-EIMS與GC-PCIMS分析。第二部份：利用酸水解及鹼（或甲醇）水解，分別針對尿液及頭髮檢體進行前處理，而後以自動化固相萃取儀(SPE)配合HCX萃取管柱之使用，將存在於尿液及頭髮檢體中所含之可待因、嗎啡及6-乙醯嗎啡等成分萃取出來，並以甲基三甲矽基三氟乙醯胺(N-methyl-N-trimethylsilyltrifluoroacetamide, MSTFA)衍生劑衍生後進行GC-MS分析，以探討尿液與頭髮檢體中鴉片類代謝物含量之分布及檢出情形。第三部份則針對目前最常見之攙加物包括有食鹽、洗手乳、漂白水、維大力汽水、明礬、自來水及重鉻酸鉀( potassium dichromate, PDC )等共七種攙加物，以三種不同比例( 5%, 10%, 15% )分別攙加於含有安非他命/甲基安非他命與MDA/MDMA之尿液檢體，之後採用TDX與生化分析儀器分別進行攙假尿液之初篩實驗，所評估之項目包括有TDX分析值、肌酐酸(creatinine)、比重、pH值、亞硝酸鹽(nitrite)、顏色等值之變化；而後，利用GC-MS儀器進行攙假尿液之確認實驗；初篩與確認實驗後所得之檢驗值再施以SPSS之統計分析。第四部份：文獻報導尿檢之結果可能會受到尿液儲存時之多項因子影響，包括尿液檢體儲存之天數、儲存溫度、尿中葯毒物之代謝物濃度與容器種類等。本研究的目的在進一步探討尿液檢體儲存條件與環境對尿檢結果是否有影響，以及這些主因子之間的交互影響效應。首先利用L16215直交表實驗設計法，經進行GC-MS以分析檢定儲存尿液中THC-COOH、AP、MA、MDMA與MDA等毒品之主因子效應與主因子交互作用後，再以L64421直交表實驗設計法，針對尿中之上述等五種毒品，探討各項儲存主成分因子之最佳水準，最後綜合L16215 與L64421兩種GC-MS之直交表實驗數據，並利用SPSS軟體進行ANOVA分析，以得到最佳化之尿液儲存條件。第五部份：針對可能殘留於現場空氣中之大麻煙成分，利用吸附管收集後，經脫附後再利用GC-MS以進行確認分析。
主要結果分述如下：第一部份：KT及NK之衍生物可被傳統之GC-EIMS成功地鑑驗出來，同時亦使用GC-PCIMS進一步分析KT及NK結構上特有之氯原子所呈現出之同位素特性質譜圖（氯35與氯37二者原子之自然豐度比為3比1），其可藉以輔助確認結果。第二部份：分析採自監所之來自同一人之尿液及頭髮檢體共30人，實驗結果顯示30個尿液檢體均檢出嗎啡，但未檢出6-乙醯嗎啡；頭髮檢體亦均檢出嗎啡，但只有19個檢出含6-乙醯嗎啡。尿液檢體之嗎啡與頭髮檢體之6-乙醯嗎啡，二者含量之相關性並不高。第三部份：含安非他命類藥物之尿液檢體當攙加七種攙加物後，其初篩實驗之TDx值與確認實驗之GC-MS值均變小，其中以漂白水對於初篩實驗之TDx檢出值與確認實驗之GC-MS檢出值的影響最為嚴重；因此可推知，在待測尿液檢體中攙加不同攙假物質確會干擾鑑驗結果之判斷。第四部份：兩種直交表實驗所得到最佳化之尿液儲存條件如下：五種藥物除了THC-COOH最好在40天內完成鑑驗外，餘四種均須在90天內；五種藥物中AP、MA、THC-COOH以儲存於玻璃容器為最佳條件， MDA與MDMA則以儲存於PP材質容器為最佳之儲存環境。至於儲存時之濃度與溫度，AP、MA、MDA、MDMA、THC-COOH等5種成分中皆以1.25倍之各自的法定檢驗閾值及-20℃為最佳之儲存條件。第五部份：殘留於空氣中之大麻煙之主成分THC，可藉由含Tenax-TA之吸附管吸附、脫附後被GC-MS檢出。所檢出之THC其平均脫附效率為89%，偵測極限為0.1 μg m-3，相當於1.09 mg的大麻葉在3.0m × 2.4m × 2.7m之無通風設備小房間內的抽食產量。
上述五部分對於存在於尿液、頭髮及現場空氣中之管制藥品檢測方法暨所得之實驗結果皆可提供實務鑑識工作之參考。

Abstract
A variety of drugs including opiates, amphetamines, MDMA, MDA, ketamine, and marijuana are nowadays commonly abused in Taiwan. This thesis aimed to analyze such controlled substances in samples of urine, head hair, and indoor air using various kinds of pretreatment strategies coupled to gas chromatography-mass spectrometry (GC-MS).
This work includes five parts. Part I: An analytical scheme using GC-MS assisted by precedent liquid-liquid extraction (LLE) and chemical derivatization with petafluorobenzoyl chloride (PFBC) is described for the simultaneous determination of ketamine (KT) and its major metabolite, norketamine (NK), in urine specimens. Part II: Preceding the extraction procedure, the urine and hair samples after adequate preparation were treated, respectively, with acid, alkaline, and methanol hydrolysis. The solid-phase extraction (SPE) instrument equipped with a HCX column was employed to recover codeine, morphine, and 6-acetylmorphine from both samples. The extracted solution was dried, devirated by MSTFA, and followed by GC-MS analysis with the purpose to investigate qualification and quantification of opiates and the metabolites in urine and hair. Part III: In this study, a total of seven items including table salt, liquid soap, chlorine bleach, Vitali drinking soda water, tap water, potassium dichromate, and aluminum ammonium sulfate were adulterated respectively with three different concentrations (5%, 10%, and 15%) to urine samples containing morphine/codeine, MDA/MDMA, or AP/MP. The adulterated urine samples were screened using TDx and Beckman LX/20 instrument. The adulterating impact on urine analysis of abused drugs was evaluated as a function of TDx values, creatinine, gravity, pH, nitrite, color, and odor. GC-MS analysis was then followed for confirmatory purpose. The effects and variations were analyzed by SPSS. Part IV: The aim of this part was to optimize the storage conditions of urine samples. The five drugs including THC-COOH, AP, MA, MDMA, and MDA contained in urines were analyzed by GC-MS. Based on the raw data obtained, the optimization of storage conditions was established by using the orthogonal arrays of L64421 and L16215, coupled with the statistical analyses of ANOVA by SPSS software. Part V: A simple and affordable method for the determination of Δ9-tetrahydrocannabinol (Δ9-THC) in indoor air was described. A personal air-sampler pump fitted with the GC liner-tube packed with Tenax-TA adsorbent was used for air sampling. The GC-adsorbent tube was placed in the GC injector port and desorbed directly, followed by GC-MS analysis for the determination of Δ9-THC in indoor air.
Major results of the five are briefly described as the following. Part I: The derivatives of KT and NK in urine specimens can be successfully identified. The mass spectra can always distinctly reflect the natural-abundance ratio of Cl35 and Cl37 isotopes, i.e., Im/z M+!/Im/z M+3≒3:1, thereby facilitating the confirmation of KTs. Part II: A total of 30 paired samples of hair and urine from the same individual were analyzed. All the 30 paired samples were concluded to be morphine-positive, with emphasizing that the 6-acetylmorphine couldn’t be detected from the urine. The percentage of 6-acetylmorphine detected in the inmates’ hair samples with methanol hydrolysis were found to be 63.3% (19 out of 30). Part III: All the seven tested adulterants would render significant impacts on forensic amphetamines urinalysis by TDx screening and GC-MS confirmatory tests, with chlorine bleach being most likely to give false negatives, especially on near-cutoff specimens. Part IV: For the optimized period of storage, the THC-COOH was found to be within 40 days, and the other four were within 90 days. The best raw materials built into containers for the AP, MA, and THC-COOH was glass, and PP material for MDMA and MDA. All five drugs had an optimized storage condition of temperature at -20℃. As for the factor of drug concentration, the five drugs at 1.25 times of their respective cut-off value were revealed to be the best. Part V: The characteristic Δ9-THC peak in chromatogram can serve as the indicator of marijuana. The average desorption efficiency and limit of detection for Δ9-THC were 89% and 0.1 μg m-3, respectively, approximately needing 1.09 mg of marijuana leaves smoked in an unventilated closed room (3.0m × 2.4m × 2.7m) to reach this level.
The proposed methods and thus obtained results in this thesis would provide useful information for practical forensic drug testing.

Contents

Abstract…………………………………………………………………..I
摘要…………………………………….............………………...............................III
Delication..................................................................................................................V
Contents………………………………………………………..…………..…...…..VI
List of Tables……………………………………………………………..…….......X
List of Figures………………………………………………………..………...…..XII

Chapter 1    Background
1.1. CURRENT DRUG ABUSE SITUATION IN TAIWAN
1.1.1    Introduction……………………………………………………………….1
1.1.2    Statistics on drugs and crime…………………………………………….1
1.2. INITIATION AND/OR SIGNIFICANCE OF THE
RESEARCH ISSUES………………………………………………3
1.2.1. Ketamine, opiates, and its metabolites in biological specimens….…….3
1.2.2. Impacts of adulterants on amphetamines and opiates urinalysis ……..4
1.2.3. Optimization study of storage condition for amphetamine  methamphetamine, marijuana, MDMA, and MDA in urine…………..4
1.2.4. Determination of Δ9-tetrahydrocannabinol in indoor air as an
     indicator of marijuana cigarette smoking…………………………….....5
1.3. PROPERTIES AND METABOLISM OF ABUSED DRUGS STUDIED IN THIS THESIS……………………………………….…......6
1.3.1. Amphetamine-like…………………………………………....…….…......6
1.3.2. Opiate-like……………………………………………………….….……..9
1.3.3. Marijuana…………………………………….……………………..……10
1.3.4 . Ketamine……………………………………………………….….……..11
References....…………………………………………………………………..…….12

Chapter 2    GC-MS Analysis of Ketamine and Its Metabolites in
Urine Samples
2.1.  INTRODUCTION……………………………………...…....…....13
2.2.  MATERIALS AND METHOD……………………………...……14
2.2.1.  Chemicals………………………………………………..…….….…….14
2.2.2.  Sample preparation………………………………………….….….…..15
2.2.3.  Gas Chromatography-Mass spectrometry…………………………..16
2.3. RESULTS AND DISCUSSION……………………………….......17
2.3.1. Efficacies of derivatization of KT and NK with PFBC…………...…..17
2.3.2. Selection of qualifier and quantifier ions...............................................19
2.3.3. Quantitation..............................................................................................20
2.3.4. Limits of detection (LODs) and limits of quantitation (LOQs)………..……22
2.3.5. Analyte recoveries indicative of method performance…………….….22
2.3.6. Auxiliary GC-MS analysis using positive ion chemical ionization
(CI)……………………………………………………………………….22
2.3.7. Case study………………………………………………………..………23
2.4. CONCLUSIONS…………………………………………….…….23
References……………………………………………………………….…………25

Chapter 3    Detection of Morphine, Codeine, and 6-acetylmorphine
 in Human Urine and Hair by GC-MS
3.1. INTRODUCTION…………………………………………….…….…..…35
3.2. MATERIALS AND METHOD……………………………..….………..37
3.2.1  Urine and hair samples…………………………………….………….37
3.2.2  Chemicals………………………………………………………………37
3.2.3  Preparation of standard solutions………………………….…………37
3.2.4.  Urine samples with/without acid hydrolysis treatment…….……….38
3.2.5.  Decontamination and digestion of hair samples………….……...….38
3.2.6.  Derivatization……………………………………………………....….39
3.2.7.  GC-MS analysis………………………………………………….……39
3.2.8.  Calibration………………………………………………………..……40
3.3. RESULTS AND DISCUSSION…………………………….……….…...41
3.3.1. Qualitative analysis………………………………………………...……41
3.3.2. Quantitative analysis………………………………………….…..…….41
3.3.3. Real case study…………………………………………………….….…43
3.3.4. Determination of cutoff concentration………………………….…..…..43
3.4. CONCLUSIONS…………………………………………….….…44
References……………………………………………………………….…..….…..46

Chapter 4    Impacts of Adulterants on Amphetamines Urinalysis
4.1. INTRODUCTION………………………………………….…………..….57
4.2. MATERIALS AND METHOD……………………………………….....58
4.2.1. Urine collection, spiking and adulteration………………………...…..59
4.2.2. FPIA screening test………………………………………………..……61
4.2.3. GC-MS confirmatory test………………………………………..……61
4.3. RESULTS AND DISCUSSION………………………….…….…63
4.3.1. Effects of adulterants on FPIA screening test……………..…..…..…63
4.3.2. Effects of adulterants on GC-MS confirmatory test………………...66
4.3.3. Comparison of TDx and GC-MS data with respect to effects of adulterants…………………………………………………….………71
4.4. CONCLUSIONS…………………………………………….……75
References………………………………………………………………………...77

Chapter 5    Optimization of Storage Condition for Amphetamine, Methamphtamine, Marijuana, MDMA, and MDA in
Urine by Orthogonal Array Design and GC-MS Analysis
5.1.    INTRODUCTION………………………………….…….……….91
5.2.    MATERIALS AND METHOD……………………………..…….…….93
5.2.1.  Chemicals……………………………………………………….……93
5.2.2.  Preparations…………………………………………………….……93
5.2.3.  Urine samples…………………………………………………….….94
5.2.4.  SPE (solid phase extraction) procedure……………………………95
5.2.5.  Derivatization………………….……………………………….…….95
5.2.6.  GC-MS analysis…………………………………………….….…….96
5.2.7.  Optimization study by Orthogonal array design………….…….…96
5.3.    RESULTS AND DISCUSSION………………………………...….…..97
5.3.1.  Selection of qualifier and quantifier ions……………………...……97
5.3.2.  Linearity and LOD/LOQ………………………………………..…..97
5.3.3.  Recovery of SPE……………………………………….………….…98
5.3.4.  Blind test result…………………………………………….….….….98
5.3.5.  Optimization using the L16215 and L64421orthogonal array…...…..98
5.4.    CONCLUSIONS……………………………………..………..….….….100
References…………………………………………………………..…..…….…102

Chapter 6    Determination of Δ9-tetrahydrocannabinol in Indoor
Air as an Indicator of Marijuana Cigarette Smoking
Using Adsorbent Sampling and In-injector Thermal
          Desorption GC-MS
6.1    INTRODUCTION……………………………………….. ……..123
6.2. MATERIALS AND METHOD………………………… ……....124
6.2.1. Chemicals and materials………………………………………… .…124
6.2.2. Generation of simulated marijuana smoke………………… ….…..125
6.2.3. Sampling of indoor air……………………………………….…….…125
6.2.4. Thermal desorption and GC-MS analysis…………………….…….126
6.2.5. Calibraton and method validation…………………………….……..126
6.2.6. Marijuana smoke from a casework………………………...…….….128
6.3. RESULTS AND DISCUSSION……………………………….…128
6.3.1. Quantitative analysis……………………………………………..…....128
6.3.2. Quantitative analysis……………………………………………….….129
6.3.3. PCA analysis……………………………………………….….….….…131
6.3.4. Real sample analysis……………………………………………….…..132
6.4. CONCLUSIONS……………………………………………….…………133
References…………………………………………………………..……….……134

Chapter 7    Concluding Remarks and Perspectives
7.1.    CONCLUDING REMARKS………………….………………….143
7.1.1.  Analysis of ketamine and its metabolites in urine specimens.….….143
7.1.2.  Detection of morphine, codeine, and 6-acetylmorphine in human
urine and hair by GC-MS…………………..……………….………144
7.1.3.  Impacts of adulterants on amphetamines urinalysis……….………144
7.1.4.  Optimization of storage for abused drugs using orthogonal array design………………………………………………..…………….…..144
7.1.5.  Investigation of marijuana smoke and correlated to the levels from authentic smoking………………………….…………….……….…..145
7.2.    PERSPECTIVES……………………………………….…………..…..…..146
7.2.1.  Effects of drugs of abuse on the brain……………………………….146
7.2.2.  Future direction………………………………………...……….…….147

APPENDIX A…………………………………...……………………….…………148

List of Tables
Table  1.1  The type of drugs involved in drug abuse cases in 2006……….….…..…3
Table  1.2  Locations or spots to seize drugs in drug abuse cases in 2006….………..5
Table  2.1  The retention times (RTs) obtained upon the GC-MS analyses of PFBC-derivatized and underivatized ketamine analytes and internal standards……………………………………………………….……..…27
Table  2.2  Qualifier and quantifier ions (m/z) selected for PFB-KT, PFB-KT-d4, PFB-NK, and PFB-NK-d4…………………………………….……..…28
Table  2.3  Method limits of detection (LODs) and method limits of quantitation (LOQs) for the total analysis of KT and NK in urine via GC-EIMS and GC-PCIMS, respectively…………………………………………….….29
Table  2.4  Results obtained upon the total analyses of four real-case samples, all definitely involving ketamine administration……………………….….30
Table  3.1  SPE procedure for urine and hair specimens…………………..…….…48
Table  3.2  Retention times (RTs) and Qualifier / quantifier ions (m/z)
selected for analytes………………………………………………..…..49
Table  3.3  Results of the LOD, LOQ, linearity ranges, linear correlation
coefficient (r2) for MSTFA-derivatives in urine and hair specimens…………………………………………………….…….…..50
Table  3.4  SPE recoveries for urine specimens…………………………………....51
Table  3.5  SPE recoveries for hair specimens with NaOH and methnol digestion..52
Table  3.6  Cutoff concentrations of opiates established by DoD, DHHS, DHHS,
and proposed by Taiwan Government Agency…………………….…..53
Table  3.7  Cutoff concentrations of opiates in hairs reported in literatures…….…54
Table  4.1  TDx levels of sum-MA/AP and sum-MDMA/MDA a,b,c observed for unadulterated (control) and adulterated urine spikes each formerly fortified with 1250 (i.e., 625 + 625) ng mL-1 of the appropriate drug pair………………………………………………………………..……79
Table  4.2  Calibration equations, linear working ranges, linear correlation coefficients (r2), and method limits of detection and quantitation (LODs/LOQs) for the determination of APs in urine by SPE and HFBA-ChD followed by GC-EIMS SIM…………………….….……80
Table  4.3    GC-MS determined APs concentrations (ng mL-1) a,b,c in
unadulterated (control) and adulterated urine spikes each formerly fortified with 1250 (i.e., 625 + 625) ng mL-1 of MA/AP or MDMA/MDA…….………………………………………….….…….81
Table  4.4  Comparison of TDx and GC-MS found sum-MA/AP and sum-MDMA/MDA concentrations in unadulterated and adulterated
urine spikes………………………………….…………………..…….82
Table  4.5  Comparison of TDx sum-APs and corresponding GC-MS
sum-MA/AP or sum-MDMA/MDA a,b obtained before and after
 adulteration of six case urine specimens previously confirmed as
           MA-positive or MDMA-positive…...............……………..….….........83
Table  5.1  SPE procedures for urine specimens (AP, MA, MDA, and MDMA)..104
Table  5.2  SPE procedures for urine specimens (THC-COOH)…………………105
Table  5.3  Qualifier / quantifier ions (m/z) selected for analytes……………..…106
Table  5.4  LOD/LOQ, linearity range, linear correlation coefficient (r2),
and recovery of analytes…………………………………………...…107
Table  5.5  L16215 statistical results for HFB-AP…………………………………108
Table  5.6  L16215 statistical results for HFB-MA…………………………...……109
Table  5.7  L16215statistical results for HFB-MDA……………………………….110
Table  5.8  L16215statistical results for HFB-MDMA……………………….…….111
Table  5.9  L16215statistical results for BSTFA:TMCS(99:1)-THC-COOH…...….112
Table  5.10 Drug derivatives recovery based on the L64421 major effect response...113
Table  5.11 Optimized storage conditions for urine specimens with
drug derivatives……………………..…………………………….…..114
Table  6.1  Major components in marijuana and tobacco smoke analyzed by GC-MS ………………………………………………….………..….136
Table  6.2  Analytical performance of different calibration schemes……………137
Table  6.3  The content of Δ9-THC in marijuana smoke and methanol extract
from 15 different marijuana plant leaves…………………………….138








List of Figures
Fig. 1.1     Drug cases in prosecution during the past ten years…..………………..….2
Fig. 1.2   Metabolism of amphetamines…………………………………………..….7
Fig. 1.3   Metabolism of methamphetamines………………………………….……..8
Fig. 1.4   Metabolism of MDMA………………………………………….…………8
Fig. 1.5.1 Metabolism of opiates………………………………………………….…..9
Fig. 1.5.2 Metabolic pathways for heroin and acetylcodeine………….……………..10
Fig. 1.6   Metabolism of delta-9-Tetrahydrocannabinol (THC)…………………….10
Fig. 1.7  Metabolism of ketamine………………………………………..…….……11
Fig. 2.1  The mass spectra obtained upon the GC-EIMS full scan of (a) PFB-KT,
and (b) PFB-KT-d4…………………..……………………….………..…..31
Fig. 2.2  The mass spectra obtained upon the GC-EIMS full scan of (a) PFB-NK,
        and (b) PFB-NK-d4…………………..……………………….…………...32
Fig. 2.3  The mass spectra obtained upon the GC-PCIMS full scan of (a) PFB-KT,
and (b) PFB-KT-d4…………………………..……………….………..…..33
Fig. 2.4  The mass spectra obtained upon the GC-PCIMS full scan of (a) PFB-NK,
        and (b) PFB-NK-d4…………………………………….……………..…...34
Fig. 3.1  The TIC chromatogram obtained upon the GC-EIMS full scan of a
pretreated urinary……………………………….……………….…………55
Fig. 3.2  The mass spectra of (a) MSTF- codeine-D6 and MSTF- codeine,
(b) MSTF- morphine- D6 and MSTF-morphine, and (c) MSTF-
6-acetylmorphine- D6 and MSTF-acetylmorphine………………...…..….56
Fig. 4.1  The isotope dilution GC-EIMS SIM chromatogram obtained for the SPE/HFBA-ChD of a real-case urine specimen containing MA/AP….…. 85
Fig. 4.2     Mass spectra of (a) HFB-AP, (b) HFB-AP-d8, (c) HFB-MA, and (d) HFB-MA-d8………………………………………………...…………….86
Fig. 4.3  The isotope dilution GC-EIMS SIM chromatogram obtained for the PE/HFBA-ChD of a case urine specimen containing MDMA/MDA……..88
Fig. 4.4  Mass spectra of (a) HFB-MDA, (b) HFB-MDA-d5, (c) HFB-MDMA,
 and (d) HFB-MDMA-d5………………………………….………..…..…89
Fig. 5.1.1  The TIC chromatogram obtained upon the GC-EIMS full scan of a pretreated urinary…………………….…………………….….………115
Fig. 5.1.2 The mass spectrum of the HFB-AP-D5………………………….…....…116
Fig. 5.1.3 The mass spectrum of the HFB-AP……………………..….…….…...…116
Fig. 5.1.4 The mass spectrum of the HFB-MA-D8…………………….…….…..…117
Fig. 5.1.5 The mass spectrum of the HFB-MA………………………….…….……117
Fig. 5.1.6 The mass spectrum of the HFB-MDA-D5……………………...….…….118
Fig. 5.1.7 The mass spectrum of the HFB-MDA……………………….…………118
Fig. 5.1.8 The mass spectrum of the HFB-MDMA-D5…………………….……..119
Fig. 5.1.9 The mass spectrum of the HFB-MDMA………………………….……119
Fig. 5.2.1 The TIC chromatogram obtained upon the GC-EIMS full scan of a
pretreated urinary……….………………………………..………….…120
Fig. 5.2.2 The mass spectrum of the BSTFA:TMCS (99:1)-THC-COOH-D9……121
Fig. 5.2.3 The mass spectrum of the BSTFA:TMCS (99:1)-THC-COOH…..……121
Fig. 5.3  CV% (n=3) and storage time (0-167 days) of blind samples………..…122
Fig. 6.1  The GC-MS total ion chromatograms………………………………….139
Fig. 6.2  Expanded portion of GC-MS total ion chromatograms………………...140
Fig. 6.3  Two dimensional plot of PCA results of marijuana smoke and
tobacco smoke………………..…..………………………………….…141
Fig. 6.4  The GC-MS total ion chromatograms of indoor air suspected
of containing marijuana smoke from a KTV stateroom…………….......142

                                

chapter1
References
[1] 96年反毒報告書(http://www.tnh.moj.gov.tw/ct.asp?xItem=91955&ctNode=7868&mp=005)
[2] 行政院衛生署管制藥品管理局(http://www.nbcd.gov.tw/home/home/index.aspx)
[3] R. Schwarzhoff, J.T. Cody, J. Anal. Toxicol. 17 (1993) 14.
[4] S.L. Mikkelsen, K.O. Ash, Clin. Chem. 34 (1988) 2333.
[5] J.T. Cody JT, Forensic Sci. Rev. 2 (1990) 63.
[6] B. D. Paul, R.M. McKinley, J.K. Walsh, T.S. Jamir, M.R. Past, J. Anal. Toxicol. 17 (1993) 378.
[7] R.A. Rockerbie, D.J. Campbell, Clin. Biochem. 11 (1978) 77.
[8] U.S. Food and Drug Administration, Guidance for Industry, Bioanalytical Method Validation, Center for Drug Evaluation and Research (CDER), Rockville, May 2001
[9] http://www.cscq.ch/agsa/E/EAPP2.htm
[10] C. Staub, M. Marset, A. Mino, P. Mangin, Clin. Chem. 47 (2001) 301.
[11] R.C. Baselt, Disposition of Toxic Drugs and Chemicals in Man, seventh ed. (2004), Chemical Toxicology Institute, Foster city, CA.
chapter2
References
[1] A. Mozayani, Forensic Sci. Rev. 14 (2002) 123.
[2] R.C. Baselt, Chemical Toxicology Institute, Foster city, CA.
[3] A.C. Moffat, M.D. Osselton, B. Widdop, Clarke's Analysis of Drugs and Poisons, third ed. (2004), Pharmaceutical Press, London.
[4] DEA Press Release, DEA to control "special K" for the first time, July 13 (1999).
[5] Erowid, The vaults of Erowid, http://www.erowid.org/chemicals/ketamine/ketamine_testing.shtml, Jan 10 (2003).
[6] M.M. Kochhar, Clin. Toxicol. 11 (1977) 265.
[7] J.N. Davisson, J. Chromatogr.146 (1978) 344.
[8] F.N. Pitts, L.S. Yago, O. Aniline, J. Chromatogr. 193 (1980) 157.
[9] R.I. Stiller, P.G. Dayton, J.M. Perel, C.C. Hug, J. Chromatogr. 232 (1982) 305.
[10] M.L. Olmos-Carmona, M. Hernandez-Carrasquilla, J. Chromatogr. B 734 (1999) 113.
[11] A.S. Gross, A. Nicolay, A. Eschalier, J. Chromatogr. B 728 (1999) 107.
[12] M. Licata, P. Pierini, G. Popoli, J. Forensic. Sci. 39 (1994) 1314.
[13] Y. Gaillard, G. Pepin, J. Forensic Sci. 43 (1998) 435.
[14] J.-O. Svensson, L.L. Gustafsson, J. Chromatogr. B 678 (1996) 373.
[15] F. Sporkert, F. Pragst, Forensic Sci. Int. 107 (2000) 129.
[16] R. Sams, P. Pizzo, J. Anal. Toxicol. 11 (1987) 58.
[17] M.M. Kochhar, L.T. Bavda, R.S. Bhushan, Res. Comm. in Chem. Pathol. and Pharmacol. 14 (1976).
[18] S. Cohen, editor, Toxi-News [http://www.erowid.org] 21(1) (2002).
[19] S.C. Peyton, A.T. Couch, R.O. Bost, J. Anal. Toxicol. 12 (1988) 268.
[20] M.L. Olmos-Carmona, M. Hernandez-Carrasquilla, J. Chromatogr. B 734 (1999) 113.
[21] T. Chang, A.J. Glazko, Anesthesiol. 36 (1972) 401.
[22] Y. Yanagihara, M. Ohtani, S. Kariya, K. Uchino, T. Aoyama, Y. Yamamura, T. Iga, J. Chromatogr. B 746 (2000) 227.
[23] S. Bolze, R. Boulieu, Clin. Chem. 44 (1998) 5600.
[24] E.D. Kharasch, R. Labroo, Anesthesiol. 77 (1992) 1201.
[25] R.H. Liu, Elements and Practice in Forensic Drug Urinalysis, Central Police University Press, Taiwan, ROC (1994).
[26] K.A. Moore, J. Sklerov, B. Levine, A.J. Jacobs, J. Anal. Toxicol. 25 (2001) 583.
[27] S.M. Wang, Y.S. Giang, Y.C. Ling, J. Chromatogr. B 759 (2001) 17.
[28] B.A. Goldberger, M.A. Huestis, D.G. Wilkins, Forensic Sci. Rev. 9 (1997) 59.
[29] Analytical Methods Committee, Analyst 112 (1987) 199.
chapter3
References
[1] S.Y. Yeh, C.W. Gorodetzky, R.L. McQuinn, Pharmacol. Exp. Ther.196 (1976) 249.
[2] R.H. Liu, ,Handbook of workplace drug testing,Washington, (1995) 225.
[3] M. Katagi, M. Nishikawa, M. Tatsuno, A. Miki, H. Tsuchihashi, J. Chromatogr. B 751 ( 2001) 177.
[4] C. Staub, M. Marset, A.Mino, P. Mangin, Clin Chem 47 (2001) 301.
[5] B.D. Paul, J.M. Mitchell, L.D. Mell, J. Irving, J. Anal. Toxicol. 13 (1989) 2.
[6] J. Fehn, G. Megges, J. Anal. Toxicol. 9 (1985) 134.
[7] E.J. Cone, P .Welch, J.M. Mitchell, B.D. Paul, J. Anal. Toxicol. 15 (1991) 1.
[8] C.L. O'Neal, A. Poklis, J. Anal. Toxicol. 21 (1997) 427.
[9] C.L. O'Neal, A. Poklis, Forensic Sci. Int. 95 (1998) 1.
[10] C.L. O'Neal, A. Poklis, Drug Alcohol Depend. 65 (2001) 37.
[11] C. Girod, C. J. Anal. Toxicol. 25 (2001) 106.
[12] A.I. Al-Asmari, R.A. Anderson, J. Anal. Toxicol. 31 (2007) 394.
[13] T.B. Vree, C.P. Verwey-van Wissen, Biopharm. Drug Dispos. 13 (1992) 445.
[14] K. Oguri, N. Hanioka, H. Yoshimura, Xenobiotica. 20 (1990) 683.
[15] Y. Nakahara, Arch. Toxicol. 66 (1992) 669.
[16] Y. Nakahara, R. Kikura, K. Takahashi, J. Chromatogr. B Biomed. Appl. 657 (1994) 93.
[17] M. Montagna, C. Stramesi, C. Vignali, A. Groppi, A. Polettini, Forensic Sci. Int. 107 (2000) 157.
[18] A. Polettini, C. Stramesi,C. Vignali, M. Montagna, Forensic Sci. Int. 84 (1997) 259.
[19] B.A. Goldberger, E.J. Cone, T.M. Grant, Y.H. Caplan, B.S. Levine, J.E. Smialek, J. Anal. Toxicol. 18 (1994) 22.
[20] L. Skender, V. Karacić, I. Brcić, A. Bagarić, Forensic Sci. Int. 125 (2002) 120.
[21] C. Staub, Forensic Sci. Int. 70 (1995) 111.
[22] B. D. Paul, T. Eric, L. Smith, Clin. Chem. 45 (1999) 510.
chapter4
References
[1] A. Hoffman, Steal This Urine Test: Fighting Drug Hysteria in America; Penguin Book: New York, 1987; 183.
[2] B.I. Podkowik, M.L. Smith, R.O. Pick, J. Anal. Toxicol. 11 (1987) 215.
[3] P.A. Lambert, P.A.Woodbridge, P.N. Botie, Clin. Chem. 33 (1987) 977.
[4] J.T. Cody, R.H. Schwarzhoff, J. Anal. Toxicol. 13 (1989) 277.
[5] H.J. Kim, E. Cerceo, Clin. Chem. 22(1976) 1935.
[6] S.L. Mikkelsen, K.O. Ash, Clin. Chem. 34 (1988) 2333.
[7] D. Vu, Clin. Chem. 31 (1985) 658.
[8] M.Warner, Clin. Chem. 35 (1989) 648.
[9] Mandatory Guidelines for Federal Workplace Drug Testing Programs Federal Register, 2004; 19644.
[10] J.T. Cody, Forensic Sci. Rev. 2 (1990) 63.
[11] L.S. Tsai, M.A. ElSohly, S.F. Tsai, T.P. Murphy, B. Twarowska, S.J. Salamone, J. Anal. Toxicol. 24 (2000) 708.
[12] J. T. Cody, S. Valtier, J. Kuhlman, J. Anal. Toxicol. 25 (2001) 572.
[13] R. Schwarzhoff, J.T. Cody, J. Anal. Toxicol. 17 (1993) 14.
[14] C. Baiker, L. Serrano, B. Lindner, J. Anal. Toxicol. 18 (1994) 101.
[15] A.H Wu, B. Bristol, K. Sexton, G. Cassella-McLane, V. Holtman, D.W. Hill, Clin. Chem. 45 (1999) 1051.
[16] L.S. Tsai, M.A. ElSohly, T. Dubrovsky, B. Twarowska, J. Towt, S.J. Salamone, J. Anal. Toxicol. 22 (1998) 474.
[17] J.M. Holler, T.Z. Bosy, K.L. Klette, R. Wiegand, J. Jemionek, A. Jacobs, J. Anal. Toxicol. 28 (2004) 489.
[18] S.M. Wang, Y.C. Ling, L.C. Tsai, Y.S. Giang, J. Chromatogr. A 715 (1995) 325.
[19] S.M. Wang, Y.S. Giang, Y.C. Ling, J. Chromatogr. B 759 (2001) 17.
[20] S.M. Wang, Y.S. Giang, Y.C. Ling, Forensic Sci. J. 1 (2002) 47.
[21] Y.S. Giang, S.M. Wang, H.L. Chiang, Forensic Sci. J. 2 (2003) 27.
[22] S.M. Wang, Y.C. Ling, Y.S. Giang, Forensic Sci. J. 2 (2003) 5.
[23] S.M. Wang, T.C. Wang, Y.S. Giang, J. Chromatogr. B 816 (2005) 131.
[24] P.R. Stout, C.K. Horn, K.L. Klette, J. Anal. Toxicol. 26 (2002) 253.
[25] M.A. Przekop, J.E. Manno, G.W. Kunsman, K.R. Cockerham, B.R. Manno, J. Anal. Toxicol. 15 (1991) 323.
[26] A. Poklis, K.V. Hall, J. Still, J. Anal. Toxicol. 15 (1991) 101.
[27] J. Hsu, C. Liu, C.P. Hsu, W.I. Tsay, J.H. Li, D.L. Lin, R.H. Liu, J. Anal. Toxicol. 27 (2003) 471.
[28] H. Zhao, R. Brenneisen, A. Scholer, A.J. McNally, M.A. ElSohly, T.P. Murphy, S.J. Salamone, J. Anal. Toxicol. 25 (2001) 258.
[29] W. Ruangyuttikarn, D.E. Moody, J. Anal. Toxicol. 12 (1988) 229.
[30] S.D. Pearson, K.O. Ash, F.M. Urry, Clin. Chem. 35 (1989) 636.
[31] W. Bronner, P. Nyman, D. von Minden, J. Anal. Toxicol. 14 (1990) 368.
[32] P. Kintz, V. Cirimele, A. Tracqui, P. Mangin, J. Chromatogr. B 670 (1995) 162,.
[33] E. Han, W. Yang, J. Lee, Y. Park, E. Kim, M. Lim, H. Chung, Forensic Sci. Int. 152 (2005) 73.
[34] S.L. Chou, M.H. Yang, Y.C. Ling, Y.S. Giang, J. Chromatogr. B 799 (2004) 37.
chapter5
References
[1] B.D. Paul, R.M. McKinley, J.K.J. Walsh, T.S. Jamir, M.R. Past, J. Anal. Toxicol. 17 (1993) 378.
[2] R.A. Rockerbie, D.J. Campbell, Clin. Biochem. 11 (1978) 77.
[3] Guidelines for the Requirements for the Competence of Providers of Proficiency Testing Schemes, ILAC-G13, 2000.
[4] General Requirements for the Competence of Reference Material Producers, ISO/IEC Guide 34, 2000.
[5] M.J. Hippenstiel, B. Gerson, J. Anal. Toxicol. 18 (1994) 104.
[6] P.J.Oles, A.Yankovich, LC.GC, 7(1989)579. [7] P. Billot, B. Pitard, J. Chromatogr. 623 (1992) 305. [8] G.V. Kochetkova, E.G. Gladkikh, N.P .Nechaeva, R.S. Ukholina, Antibiotiki.
20 (1975) 1074.
[9] F. Feng, S. Xu, Zhongguo Zhong Yao Za Zhi 17 (1992) 282. (in Chinese) [10] B. Liu, F. Li, Z.C. Zhong, Zhongguo Zhong Yao Za Zhi 19 (1994) 220.
(in Chinese)
[11] W.G. Lan, M.K. Wong, N. Chen, Y.M. Sin, Analyst. 120 (1995) 1115. [12] J. Wu, M.K. Wong, H.K. Lee, C.N. Ong, J. Chromatogr. Sci. 34 (1996) 139.
[13] M.M. Kushnir, F.M. Urry, J. Chromatogr. Sci. 39 (2001) 129.
[14] X .Ding, J. Liao, X. Liu, Q. Wang, L.Ma, Se .Pu.16(1998):485. (in Chinese) [15] F. Ge, X. Lin, X. Huan, Q. Shi, B. Liang, J. Li, G. Zhong, Zhong Yao Cai
25 (2002) 101. (in Chinese) [16] Y .Luo, J. Zhang, L. Gong, X. Guan, Huan Jing Ke Xue 22 (2001) 95.
(in Chinese) [17] H. Uan, S. Hu, S. Lin, S. Gao, Anal Sci. 18 (2002) 701.
[18] C.T. Huang, Y.Y. Su, Y.Z. Hsieh, J. Chromatogr. A 977 (2002) 9. [19] S.C. Smith, M.G. Khaledi, Anal. Chem. 65 (1993) 193. [20] Y. Zhang, Z. Yuan, Anal. Sci.19 (2003) 945. [21] W.G. Lan, M.K. Wong, N. Chen, Y.M, Analyst. 120 (1995) 1115.
[22] R.G. Nielsen, E.C. Rickard, J. Chromatogr. 516 (1990) 99. [23] S. Hillaert, W. Van den Bossche, J. Chromatogr. A 979 (2002) 323. [24] Y .Zhang, Z. Yuan, Anal. Sci. 19 (2003) 945. [25] C.E. Lin, H.W. Chen, E.C. Lin, K.S. Lin, H.C. Huang, J. Chromatogr. A
879 (2000) 197.
[26] H.M. Liebich, R. Lehmann, C. Di Stefano, H.U. Haring, J.H. Kim, K.R. Kim, J.
Chromatogr. A 795 (1998) 388.
[27] H.G. Lee, D.M. Desiderio, J. Chromatogr. B. Biomed. Appl. 662 (1994) 35.
[28]黃敬德，博士論文，交通大學應化所，民國91年。
[29] H.B.Wan, W.G. Lan, M.K. Wong, C.Y. Mok, Y. H. Poh, J. Chromatogr. A 677 (1994) 255
[30] I.S. DuBey, Y.H. Caplan, J. Forensic Sci. 41 (1996) 845.
chapter6
References
[1] The prevention, damage, and treatment of abused substance, National Bureau of Controlled Drugs, Department of Health, Taiwan, R.O.C. (2003).
[2] S.M. Wang, Y.C. Ling, L.C. Tsai, Y.S. Giang, J. Chromatogr. A 715 (1995) 325.
[3] S.L. Chou, M.H. Yang, Y.C. Ling, Y.S. Giang, J. Chromatogr. B 799 (2004) 37.
[4] W. Huang, DE. Moody, DM. Andrenyak, EK. Smith, RL. Foltz, MA. Huestis, JF. Newton, J. Anal. Toxicol. 25 (2001) 531.
[5] T. Nadulski, F. Pragst, J. Chromatogr. B 846 (2007) 78.
[6] M.H.C. Chu, O.H. Drummer OH, J. Anal. Toxicol. 26 (2002) 575.
[7] R.A. Gustafson, E.T. Moolchan, A. Barnes, B. Levine, M.A. Huestis, J. Chromatogr. B 798 (2003) 145.
[8] N. Fucci, N. De Giovanni, M.. Chiarotti, Forensic Sci. Int. 134 (2003) 40.
[9] B. Maralikova, W. Weinmann, J. Mass Spectrom. 39 (2004) 526.
[10] A.D. Fraser, D. Worth, Forensic Sci. Int. 143 (2004) 147.
[11] P. Kintz, W. Bernhard, M. Villain, M. Gasser, B. Aebi, V. Cirimele, J. Anal. Toxicol. 29 (2005) 724.
[12] J.M. Rey, C.C. Tennant, BMJ. 325 (2002) 1183.
[13] J.D. Foley, Adolesc. Med. Clin. 17 (2006) 319.
[14] M. Kochanowski, M. Kala, Prezgl. Lek. 62 (2005) 576.
[15] R.S. Niedbala, K.W. Kardos, D.F. Fritch, K.P. Kunsman, K.A. Blum, G.A. Newland, J. Waga, L. Kurtz, M. Bronsgeest, E.J. Cone, J. Anal. Toxicol. 29 (2005) 607.
[16] J.A. Henry, W.L. Oldfield, O.M. Kon, BMJ. 326 (2003) 942.
[17] M.A. ElSohly, H. deWit, S.R. Wachtel, S. Feng, T.P. Murphy, J. Anal. Toxicol. 25 (2001) 565.
[18] M. Novotny, M.L. Lee, Experientia. 29 (1973) 1038.
[19] M.R. Lee, J. Jeng, W.S. Hsiang, B.H. Hwang, J. Anal. Toxicol. 23 (1999) 41.
[20] L.P. Lue, J.A. Scimeca, B.F. Thomas, B.R. Martin, J. Anal. Toxicol. 10 (1986) 81.
[21] A.S. Freeman, B.R. Martin, J. Pharm. Sci. 70 (1981) 1002.
[22] M. Rothberg, A. Heloma, J. Svinhufvud, E. Kahkonen, K. Reijula, Ann. Occup. Hyg. 42 (1998) 129.
[23] N.P. Kulshreshtha, S.C. Moldoveanu, J. Chromatogr. A 985 (2003) 303.
[24] S. Vainiotalo, R. Vaaranrinta, J. Tornaeus, N. Aremo, T. Hase, K. Peltonen, Environ. Sci. Technol. 35 (2001) 1818.
[25] S.M. Gordon, L.A. Wallace, M.C. Brinkman, P.J. Callahan, D.V. Kenny, Environ. Health Persp. 110 (2002) 689.
[26] W.W. Nazaroff, B.C. Singer, J. Expo. Anal. Environ. Epidemiol. 14 (2004) S71.
[27] J.F. Pankow, W. Luo, A.D. Tavakoli, C. Chen, L.M. Isabelle, Chem. Res. Toxicol. 17 (2004) 805.
[28] M. J. Baptista, P.V. Monsanto, E.G.P. Marques, A. Bermejo, S. Avila, A.M. Castanheira, C. Margalho, M. Barroso, D.N.Vieira, Forensic Sci. Int. 128 (2002) 66.
[29] D.Gieringer, J.St. Laurent, S. Goodrich, J. Cannabis Ther. 4 (2004) 7.
[30] A. Gordin, A. Amirav, J. Chromatogr. A 903 (2000) 155.
[31] Y. Takanami, M. Chida, H. Hasebe, Y. Sone, S. Suhara, J. Chromatogr. Sci. 41 (2003) 317.
[32] J.P. Zhu, B. Aikawa, Environ. Int. 30 (2004) 135.
[33] B. A. Goldberger, M.A. Huestis, D.G. Wilkins, Forensic Sci. Rev. 9 (1997) 59.
[34] H.M. Hsieh, R.J. Hou, C.S. Wei, S.W. Liu, L.H. Huang, A. Linacre, J.C. Lee, Forensic Sci. Int. 131 (2003) 53.
[35] F. Musshoff, B. Madea, Therrapeutic Drug Monitring. 28 (2006) 155.
[36] S.H. Tzing, A. Ghule, J.Y. Liu, Y.C. Ling, J. Chromatogr. A 1137 (2006) 76.

全文公開日期本全文未授權公開 (校內網路)
全文公開日期本全文未授權公開 (校外網路)

簡易檢索 / 詳目顯示

相關論文