本文選題：2C-B　切入點(diǎn)：氣相色譜法　出處：《哈爾濱商業(yè)大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：2C-B(4-溴-2,5-二甲氧基苯乙胺)是一種具有致幻、興奮作用的新型濫用物質(zhì),隨著給藥劑量的增加可對人體產(chǎn)生不同程度的精神作用。最近幾年來在我國及周邊地區(qū)頻繁出現(xiàn)2C-B的身影,給人類社會造成嚴(yán)重危害,我們在與犯罪分子進(jìn)行艱苦斗爭的同時(shí),也應(yīng)對每種濫用物質(zhì)進(jìn)行深入研究,充分了解其在體內(nèi)代謝過程及中毒成癮機(jī)制,為2C-B吸食者的戒斷和臨床救治提供理論依據(jù)。本文首次對2C-B的毒理學(xué)和代謝動力學(xué)進(jìn)行系統(tǒng)的實(shí)驗(yàn)分析,為2C-B及其系列毒品的進(jìn)一步深入研究打下基礎(chǔ)。主要研究內(nèi)容及結(jié)果如下： 通過2C-B對小鼠的急性毒性實(shí)驗(yàn)研究,確定LD100約為270mg/kg、LD0約為200mg/kg、LD50為234.11mg/kg,以此為長期毒性實(shí)驗(yàn)劑量選擇提供依據(jù)。 通過對雄性、雌性大鼠分別灌胃高、中、低三個(gè)劑量2C-B藥液5個(gè)月,及停藥1個(gè)月后臟器指數(shù)、血常規(guī)、血液生化學(xué)、組織病理學(xué)指標(biāo)進(jìn)行檢測,進(jìn)行2C-B對大鼠長期毒性實(shí)驗(yàn)研究。結(jié)果顯示長期染毒對低劑量組影響微小,對高劑量組和中劑量組影響十分明顯,機(jī)體出現(xiàn)的所有變化均主要與腦、心臟、肝臟、肺、腎產(chǎn)生病變關(guān)系緊密,且這些變化在1個(gè)月內(nèi)基本不可恢復(fù),提示這些臟器可能是2C-B毒性作用的靶器官,雌、雄無明顯差異。 論文對氣相色譜測定血液中2C-B含量的方法進(jìn)行系統(tǒng)評價(jià),以質(zhì)控樣品計(jì)算,結(jié)果表明,該分析方法的專屬性、線性關(guān)系、回收率、精密度、穩(wěn)定性均良好,符合生物樣品的測定要求。根據(jù)該方法測定不同時(shí)間點(diǎn)、不同給藥劑量2C-B的血藥濃度,數(shù)據(jù)經(jīng)3P97藥代動力學(xué)軟件處理,得到相應(yīng)的藥代動力學(xué)參數(shù),由結(jié)果可知雄性、雌性大鼠口服2C-B后,各劑量組測得的半衰期與劑量均無關(guān),Cmax值和AUC值隨劑量增大成倍增加,表明2C-B在給藥劑量為10-40mg/kg范圍內(nèi)屬于線性動力學(xué),且符合一室模型。2C-B在雄性、雌性大鼠體內(nèi)Ka、Ke、T1/2Ka、T1/2Ke、Tmax無明顯差別；與雄鼠參數(shù)比較,雌鼠的AUC、Cmax值偏高,CL/f、V/f值偏低。 通過上述實(shí)驗(yàn)結(jié)果,希望能為預(yù)防2C-B對機(jī)體損傷及不同性別2C-B濫用者的治療提供參考依據(jù)。
[Abstract]:2C-BU 4- bromo-2-bromo-5-dimethoxyphenylethylamine) is a new type of substance of abuse with hallucinogenic and exciting effects. In recent years, 2C-B has frequently appeared in our country and its surrounding areas, causing serious harm to human society. While we are struggling hard with criminals, Each substance should also be thoroughly studied in order to fully understand its metabolic process in vivo and the mechanism of addiction to poisoning, To provide theoretical basis for the abstinence and clinical treatment of 2C-B users, the toxicology and metabolic kinetics of 2C-B were analyzed systematically for the first time. To lay the foundation for further study of 2C-B and its series of drugs. The main contents and results are as follows:. The acute toxicity of 2C-B to mice was studied. The results showed that the LD100 was about 270 mg / kg LD0 and about 200 mg / kg LD50 was 234.11 mg / kg, which provided the basis for the long-term toxicity experiment. The indexes of organ index, blood routine, blood biochemistry and histopathology of male and female rats were measured by intragastric administration of high, middle and low doses of 2C-B for 5 months and 1 month after withdrawal. The long-term toxicity of 2C-B to rats was studied. The results showed that the long-term exposure had little effect on the low dose group, and obvious effect on the high dose group and the middle dose group. All the changes in the body were mainly related to the brain, heart, liver and lung. The renal lesions were closely related, and these changes could not be recovered within one month, suggesting that these organs might be the target organs of 2C-B toxicity, but there was no significant difference between male and female. The method of determination of 2C-B in blood by gas chromatography was systematically evaluated and calculated by quality control sample. The results showed that the specificity, linear relationship, recovery rate, precision and stability of the method were all good. According to this method, the blood concentration of 2C-B was determined at different time points and dosages. The data were processed by 3P97 pharmacokinetic software, and the corresponding pharmacokinetic parameters were obtained. After oral administration of 2C-B in female rats, the half-life of each dose group was not related to the dose. The values of Cmax and AUC increased exponentially with the increase of dose, which indicated that 2C-B was linear kinetics in the range of dosage of 10-40 mg / kg, and was in accordance with one-compartment model .2C-B in male. There was no significant difference between female rats and female rats, but the AUC C max value of female rats was higher than that of male rats, and the V / f value of CLP / FV / f was lower in female rats than in male rats. Through the above experimental results, we hope to provide a reference for the prevention of 2C-B injury and the treatment of 2C-B abuser of different sex.
【學(xué)位授予單位】：哈爾濱商業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R749.6

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