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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳家揚(Chia-Yang Chen) | |
dc.contributor.author | I-Ting Wang | en |
dc.contributor.author | 王怡婷 | zh_TW |
dc.date.accessioned | 2021-06-15T01:15:01Z | - |
dc.date.available | 2011-09-16 | |
dc.date.copyright | 2009-09-16 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-28 | |
dc.identifier.citation | 1. United Nations Office on Drugs and Crime. 2008 World Drug Report. http://www.unodc.org/unodc/en/data-and-analysis/WDR.html; Access date: May 24, 2009.
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The determination of morphine in urine and oral fluid following ingestion of poppy seeds. Journal of Analytical Toxicology 2003, 27, (7), 449-452. 31. Kim, I.; Barnes, A. J.; Oyler, J. M.; Schepers, R.; Joseph, R. E.; Cone, E. J.; Lafko, D.; Moolchan, E. T.; Huestis, M. A. Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration. Clinical Chemistry 2002, 48, (9), 1486-1496. 32. Kacinko, S. L.; Barnes, A. J.; Kim, I.; Moolchan, E. T.; Wilson, L.; Cooper, G. A.; Reid, C.; Baldwin, D.; Hand, C. W.; Huestis, M. A. Performance characteristics of the Cozart RapiScan Oral Fluid Drug Testing System for opiates in comparison to ELISA and GC/MS following controlled codeine administration. Forensic Science International 2004, 141, (1), 41-48. 33. Wang, W. L.; Darwin, W. D.; Cone, E. J. Simultaneous assay of cocaine, heroin and metabolites in hair, plasma, saliva and urine by gas chromatography-mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications 1994, 660, (2), 279-290. 34. Huestis, M. A.; Cone, E. J. Methamphetamine disposition in oral fluid, plasma, and urine. Conference on Oral-Based Diagnostics 2006, 104-121. 35. Navarro, M.; Pichini, S.; Farre, M.; Ortuno, J.; Roset, P. N.; Segura, J.; de la Torre, R. Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH. Clinical Chemistry 2001, 47, (10), 1788-1795. 36. Samyn, N.; De Boeck, G.; Wood, M.; Lamers, C. T.; De Waard, D.; Brookhuis, K. A.; Verstraete, A. G.; Riedel, W. J. Plasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions. Forensic Science International 2002, 128, (1-2), 90-97. 37. Samyn, N.; De Boeck, G.; Cirimele, V.; Verstraete, A.; Kintz, P. Detection of flunitrazepam and 7-aminoflunitrazepam in oral fluid after controlled administration of Rohypnol (R). Journal of Analytical Toxicology 2002, 26, (4), 211-215. 38. Cone, E. J.; Hillsgrove, M.; Darwin, W. D. Simultaneous measurement of cocaine, cocaethylene, their metabolites, and crack pyrolysis products by gas-chromatography mass-spectrometry. Clinical Chemistry 1994, 40, (7), 1299-1305. 39. K.M. Hold; D. de Boer; J. Zuidmea; R.A. Maes Saliva as an analytical tool in toxicology. International Journal of Drug Testing 1996, 1-31. 40. Crouch, D. J. Oral fluid collection: The neglected variable in oral fluid testing. Forensic Science International 2005, 150, (2-3), 165-173. 41. Lillsunde, P. Analytical techniques for drug detection in oral fluid. Therapeutic Drug Monitoring 2008, 30, (2), 181-187. 42. Wood, M.; De Boeck, G.; Samyn, N.; Morris, M.; Cooper, D. P.; Maes, R. A. A.; De Bruijn, E. A. Development of a rapid and sensitive method for the quantitation of amphetamines in human plasma and oral fluid by LC-MS-MS. Journal of Analytical Toxicology 2003, 27, (2), 78-87. 43. Samyn, N.; Laloup, M.; De Boeck, G. Bioanalytical procedures for determination of drugs of abuse in oral fluid. Analytical and Bioanalytical Chemistry 2007, 388, (7), 1437-1453. 44. Scheidweiler, K. B.; Huestis, M. A. A validated gas chromatographic-electron impact ionization mass spectrometric method for methylenedioxymethamphetamine (MDMA), methamphetamine and metabolites in oral fluid. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 2006, 835, (1-2), 90-99. 45. Fucci, N.; De Giovanni, N.; Chiarotti, M. Simultaneous detection of some drugs of abuse in saliva samples by SPME technique. Forensic Science International 2003, 134, (1), 40-45. 46. Kankaanpää, A.; Gunnar, T.; Ariniemi, K.; Lillsunde, P.; Mykkänen, S.; Seppälä, T. Single-step procedure for gas chromatography-mass spectrometry screening and quantitative determination of amphetamine-type stimulants and related drugs in blood, serum, oral fluid and urine samples. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 2004, 810, (1), 57-68. 47. Wood, M.; Laloup, M.; Ramirez Fernandez Mdel, M.; Jenkins, K. M.; Young, M. S.; Ramaekers, J. G.; De Boeck, G.; Samyn, N. Quantitative analysis of multiple illicit drugs in preserved oral fluid by solid-phase extraction and liquid chromatography-tandem mass spectrometry. Forensic Science International 2005, 150, (2-3), 227-238. 48. Mortier, K. A.; Maudens, K. E.; Lambert, W. E.; Clauwaert, K. M.; Van Bocxlaer, J. F.; Deforce, D. L.; Van Peteghem, C. H.; De Leenheer, A. P. Simultaneous, quantitative determination of opiates, amphetamines, cocaine and benzoylecgonine in oral fluid by liquid chromatography quadrupole-time-of-flight mass spectrometry. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 2002, 779, (2), 321-330. 49. Maurer, H. H. Current role of liquid chromatography-mass spectrometry in clinical and forensic toxicology. Analytical and Bioanalytical Chemistry 2007, 388, (7), 1315-1325. 50. Maurer, H. H. Advances in analytical toxicology: the current role of liquid chromatography-mass spectrometry in drug quantification in blood and oral fluid. Analytical and Bioanalytical Chemistry 2005, 381, (1), 110-118. 51. Dams, R.; Huestis, M. A.; Lambert, W. E.; Murphy, C. M. Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: Influence of ionization type, sample preparation, and biofluid. Journal of American Society for Mass Spectrometry 2003, 14, (11), 1290-1294. 52. Oiestad, E. L.; Johansen, U.; Christophersen, A. S. Drug screening of preserved oral fluid by liquid chromatography-tandem mass spectrometry. Clinical Chemistry 2007, 53, (2), 300-309. 53. Concheiro, M.; de Castro, A.; Quintela, O.; Cruz, A.; Lopez-Rivadulla, M. Determination of illicit and medicinal drugs and their metabolites in oral fluid and preserved oral fluid by liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry 2008, 391, (6), 2329-2338. 54. Dams, R.; Murphy, C. M.; Choo, R. E.; Lambert, W. E.; De Leenheer, A. P.; Huestis, M. A. LC-atmospheric pressure chemical ionization-MS/MS analysis of multiple illicit drugs, methadone, and their metabolites in oral fluid following protein precipitation. Analytical Chemistry 2003, 75, (4), 798-804. 55. Cai, Y. X.; Kingery, D.; McConnell, O.; Bach, A. C. Advantages of atmospheric pressure photoionization mass spectrometry in support of drug discovery. Rapid Communications in Mass Spectrometry 2005, 19, (12), 1717-1724. 56. Boleda, M. R.; Galceran, M. T.; Ventura, F. Trace determination of cannabinoids and opiates in wastewater and surface waters by ultra-performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography A 2007, 1175, (1), 38-48. 57. Swartz, M. E. UPLC: An introduction and review. Journal of Liquid Chromatography and Related Technologies 2005, 28, (7-8), 1253-1263. 58. Langel, K.; Engblom, C.; Pehrsson, A.; Gunnar, T.; Ariniemi, K.; Lillsunde, P. Drug testing in oral fluid - Evaluation of sample collection devices. Journal of Analytical Toxicology 2008, 32, (6), 393-401. 59. Nagler, R. M.; Hershkovich, O.; Lischinsky, S.; Diamond, E.; Reznick, A. Z. Saliva analysis in the clinical setting: revisiting an underused diagnostic tool. Journal of Medical Investigation 2002, 50, (3), 214-225. 60. Niessen, W. M. A. Nubulization ionization in LC-MS. Liquid chromatography-mass spectrometry. M. Dekker: New York, 1999; p 233-283. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42503 | - |
dc.description.abstract | 使用唾液作為篩檢樣本,具有收集不具侵入性、較無侵犯隱私的優點;由於非醫護人員也能進行樣本收集,採樣時能就近進行監控,以免樣本被置換的情形。再者,唾液中之藥物及由血漿分布而來,較能反應採樣當時體內之濃度,因此使用唾液樣本在濫用藥物檢測上漸受重視。
本研究開發以電灑游離(ESI)、大氣壓化學游離法(APCI)以及光化學游離法(APPI)作為質譜儀的游離源,搭配極致液相層析與同位素稀釋技術定量唾液中四種鴉片類與代謝物、五種安非他命類、三種氟硝西泮和代謝物、五種古柯和代謝物等共17種化合物之檢驗方法。每個化合物之質譜儀參數皆分別最適化並偵測最佳之母離子(precursor ion)和兩個訊號最強的子離子(product ion),以達到四個鑑定點(identification point)的專一性要求,本研究亦發現新型的親水性作用層析管柱(hydrophilic interaction chromatography, HILIC)對17種代測藥物的滯留效果比HSS T3管柱之滯留效果差. 在樣品前處理方面,本研究將唾液樣品以兩倍體積去離子蒸餾水 (distilled and deionizationed water, DDW) 稀釋後,添加穩定同位素標定內標準品 (internal standard),並以14,800 rpm ( 16,162 ×g )高速離心20分鐘,取上清液分析,此步驟大幅減縮一般使用固相萃取所消耗的人力、時間與耗材。本研究發現,唾液基質對大多數代測藥物的離子抑制 (ion suppression) 約在28%至78%之間,前處理回收率約為81–108%。另一方面,使用管柱後分流的方式未能有效降低唾液樣本基質效應,而使用大氣壓化學游離法以及光化學游離法亦對基質效應並無改善。 17種待測藥物分別在電灑游離、大氣壓化學游離、光化學游離情況下之定量極限分別為0.11−0.87 ng/mL, 0.02–0.74 ng/mL和0.02−0.43 ng/mL,雖然APCI 及APPI 並無法改善基質效應所造成的離子訊號抑制,但是本研究之17種待測藥物在此兩種游離源下較為靈敏,因此定量極限較ESI為低。 本研究成功利用同位素標定內標準品定量唾液中微量的待測藥物,相對標準偏差及誤差大多小於百分之15;同日與異日儀器穩定性評估,誤差與相對標準偏差亦小於15%。 本研究完成開發以液相層析/質譜/質譜儀分析唾液中重要濫用藥物及代謝物之方法,探討唾液基質對於不同游離方式之基質效應,並大幅簡化唾液樣本前處理方式。利用極致液相層析每個樣本上機時間只需7.5分鐘,大幅縮短檢測所需時間並改善靈敏度,適合於短時間內分析大量唾液檢體,提高藥物濫用防制之執行力。 | zh_TW |
dc.description.abstract | Collection of oral fluid for drug testing is non-invasive, easy, and can be done under surveillance or other difficult conditions in clinics and workplace. This study analyzed four opiates and metabolite, five amphetamines, flunitrazepam and its two metabolites, and five cocaine and metabolites in the oral fluid with ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) at selected-reaction monitoring (SRM) with isotope-dilution techniques. The most intense product ions from the most abundant precursor ions were used for quantification, and the next abundant product ions were used for confirmation. A BEH-HILIC column could not retain the 17 analytes well than that in HSS-T3 column.
This study simplified the sample preparation of oral fluid. A 100-µL sample of oral fluid was diluted with two times of deionized and distilled water (DDW) then was spiked with isotope-labelled internal standards. The sample was centrifuged for 20 min at 14,800 rpm (16,162 ×g), and the supernatant was collected for analysis. The recovery of sample preparation ranged from 81% to108%. For positive electrospray ionization (ESI+), the ion suppression of most analytes ranged from 28% to 78%; a post-column flow split (1:5) did not reduce the matrix effect. For positive atmospheric pressure chemical ionization (APCI+) and atmospheric pressure photoionization (APPI+), the ion suppression of most analytes ranged from 45% to 89% and from 74% to 96%, respectively. Limits of quantification on the 17 drugs in oral fluid on ESI, APCI and APPI were ranged from 0.11−0.87 ng/mL, 0.02−0.74 ng/mL and 0.02−0.43 ng/mL, respectively. The methods were more sensitive on APCI and APPI than on ESI. Methods were validated using spiked oral fluid at three levels on the three different ionization probes. The error percentage (accuracy) and relative standard deviations (precision) of intra-day and inter-day quantifications were most smaller than 15%. This study extensively investigated the matrix effects of oral fluid on three ionization probes. The sample preparation was much simplified and the chromatographic time was only 7.5 min per run, with a sensitivity reached ppt levels. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T01:15:01Z (GMT). No. of bitstreams: 1 ntu-98-R96844006-1.pdf: 1730744 bytes, checksum: 2d09d9416e270e7eb1fc2c2b0b93a46e (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 中文摘要 I
Abstract III Chapter I. Introduction 1 1.1 The Illicit Drug Use in the World and in Taiwan 1 1.2 The Oral Fluid 4 1.3 Pharmacokinetics of Illicit Drugs 5 1.3.1 Opiates and Metabolites 5 1.3.2 Amphetamines 8 1.3.3 Flunitrazepam and Their Metabolites 10 1.3.4 Cocaine and Metabolites 10 1.4 Factors Influence Drug Concentrations in Oral Fluid 12 1.4.1 The pH of Oral Fluid 12 1.4.2 The Routes of Administration 13 1.4.3 The Collection Process 14 1.5 The Analytical Methods 15 Chapter II. Methods 21 2.1 Reagents and Materials 21 2.2 Sample Collection and Preparation 22 2.3 Chromatographic Conditions 23 2.4 Mass Spectrometry 24 2.5 Evaluation of Matrix Effect and Recovery of Sample Preparation 25 2.6 Quantification and Data Analysis 27 2.7 Quality assurance and quality control 30 Chapter III. Results 31 3.1 Chromatography 31 3.2 Evaluation of Matrix Effect and Recovery 32 3.3 Electrospray Ionization (ESI) 33 3.4 Atmospheric Pressure Chemical Ionization (APCI) 36 3.5 Atmospheric Pressure Photoionization (APPI) 38 Chapter IV. Discussion 43 Chapter V. Conclusions 49 Reference 51 Figures 57 Tables 69 Appendix 107 | |
dc.language.iso | en | |
dc.title | 以極致液相層析/串聯式質譜儀及同位素稀釋技術分析唾液中之濫用藥物 | zh_TW |
dc.title | Determination of Abused Drugs in Oral Fluid Using Ultra-Performance Liquid Chromatography/Tandem Mass Spectrometry with Isotope-Dilution Techniques | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 何國榮(Guor-Rong Her),蔡東湖(Tung-Hu Tsai) | |
dc.subject.keyword | 液相層析/質譜/質譜儀,同位素稀釋技術,電灑游離,大氣壓化學游離,光化學游離,基質效應,濫用藥物, | zh_TW |
dc.subject.keyword | UPLC/MS/MS,isotope-dilution techniques,electrospray ionization,atmospheric pressure chemical ionization,atmospheric pressure photoionization,matrix effect,illicit drugs, | en |
dc.relation.page | 108 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-07-28 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 環境衛生研究所 | zh_TW |
顯示於系所單位: | 環境衛生研究所 |
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