以毛細管電泳搭配UV偵測器檢測美沙冬替代療法病人之血液及尿液中濫用藥物:方法開發及藥物濫用情形初估

Determination of abused drugs by capillary electrophoresis with UV detection in the plasma and urine of patients in Methadone Maintenance Treatment Program: Method development and preliminary assessment of drug abuse

許玉鈴(Yuh-Ling Sheu)

指導教授 ： 李志恒

高雄醫學大學/藥學院/藥學研究所/碩士(2011年)

https://doi.org/10.6832/KMU.2011.00008

摘要

因應處理逐步上升的藥物濫用及HIV感染率，政府在2005年實施了減害計畫，包括美沙冬替代療法及針頭交換計劃。而根據過去文獻報導指出美沙冬替代療法可以降低毒癮愛滋人數，且使用非法藥物(如:鴉片類的藥物,cocaine)的比率也有下降，也指出在替代療法中越久的病人較不易再使用非法毒品，但國內外劑量的差異性令人不免懷疑替代療法的有效性，所以在本論文中將病人區分為高劑量與低劑量兩個族群，觀測是否會受到劑量的差異性導致尿液呈現陽性反應的比例較高，而依據行政院衛生署食品藥物管理局98年的濫用藥物統計資料顯示，安非他命類及海洛因的濫用情況最為嚴重，所以將安非他命類(包含安非他命及甲基安非他命)，海洛因的代謝物嗎啡及可待因列入篩檢。因此本研究利用毛細管電泳(capillary electrophoresis)建立一簡單及敏感性高之定量分析法，分離之背景電解質(BGE) 為: 80 mM tris緩衝溶液(pH 3)，內含3.3 mM CM-β-CD、10 mM α-CD及0.1% PEO，分離電壓為+ 20 kV，使用液相液相萃取法來處理血漿及尿液檢品，分析血液及尿液中是否含有其他非法藥物的存在,以及定量和分離美沙酮及代謝物EDDP的R、S form，並且與法定方法GC-MS作優缺點比較，發現尿液高低劑量組別呈現陽性反應的比例並沒有明顯的差異性，並根據實驗得到的結果與國外進行討論及比較，國內dirty urine的比例比國外還要高，且血中濃度(R)-Methadone及(R)-EDDP都比(S)-Methadone及(S)-EDDP要來得高，與國外研究的情況相反，進而推測是否因為基因代謝上的差異性導致劑量不足或是藥物交互作用等其他因素而導致較高比例的陽性反應，依據本次論文的實驗結果僅能做初步的評估，由於美沙冬替代療法之有效性需考量多方面的因素，因此必須再更進一步的研究及探討才能確認。

關鍵字

毛細管電泳 ； 美沙冬替代療法 ； 濫用藥物

並列摘要

To cope with the escalating drug abuse situation in Taiwan, the Executive Yuan has adopted the Harm Reduction Project, which mainly includes Methadone Maintenance Treatment Program (MMTP) and Needle exchange programme. According the previous studies, the MMTP could reduce the number of drug addicts with HIV/AIDS, and the rate of illicit drugs use was also declined. The patients who retented longer in the MMTP were less likely to re-use illicit drugs. There has been a big difference in the dosage used in the MMTP between Taiwan and other countries. Therefore, the effect of MMTP in Taiwan remains to be scrutinized. In this study, the patients were divided into high-dose and low-dose groups to observe if dose differences lead to difference dirty urine ratio. According to Taiwan’s FDA statistics in 2009 which shows that amphetamines and heroin were the major drug abuse problem. Thus, amphetamine, methamphetamine and the metabolites of heroin including morphine and codeine were screened from the urine and plasma of the patients. The separation of analytes were performed using a background electrolyte containing 80 mM tris(pH 3) with 3.3 mM CM-β-CD,10 mM α-CD, 0.1% PEO. The applied voltage was +20 kV. A sample pretreatment by means of liquid-liquid extraction with subsequent quantitation. The aim of the study was not only using capillary electrophoresis to analyze methadone and other illicit narcotics in plasma and urine, but also separating chiral compounds of methadone and EDDP, which were then compared with to the results of GC-MS analysis. We found that high-dose and low-dose groups had no significant difference on dirty urine ratio. Our experiment data were also compared with the U.S. dirty urine ratio. We found that the dirty urine ratio in Taiwan was higher than that in the U.S. and the concentration of (R)-Methadone and (R)-EDDP was higher than the (S)-Methadone and (S)-EDDP. The results are contrary to the results of the Western societies. Whether the genetic difference in metabolism, inadequate dosage, or other factors, such as drug-drug interaction which may led to a less effective outcome in the MMTP, deserves further investigation.

並列關鍵字

capillary electrophoresis ； Methadone Maintenance Treatment Program ； drug abuse

參考文獻

1.Amato, L.; Davoli, M.; et al, An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment 28 (2005) 321-329.

2.Farrell, M.; Gowing, L.; et al, Effectiveness of drug dependence treatment in HIV prevention. International Journal of Drug Policy 16S (2005) S67-S75.

3.Pettes, T.; Wood, E.; et al, Methadone use among HIV-positive injection drug users in a Canadian setting. Journal of Substance Abuse Treatment 39 (2010) 174-179.

4.Metzger, D. S.; Navaline, H.; et al, Drug abuse treatment as AIDS prevention. Public Health Reports 113 (1998), supplement 1.

5.Sorensen, J. L.; Copeland, A. L.; Drug abuse treatment as an HIV prevention strategy: a review. Drug and Alcohol Dependence 59 (2000) 17-31.