Distribution profile of 2,5-dimethoxy-4-bromoamphetamine (DOB) in rats after oral and subcutaneous doses

2,5-Dimethoxy-4-bromoamphetamine (DOB) is one of the potent hallucinogenic phenylalkylamines, whose ingestion has already caused several deaths reported all over the world. However, there is unsufficient information on DOB properties based on controlled pharmacokinetic studies available. The aim of this study was to clarify the distribution profile of DOB and its phenolic metabolite 2-methoxy-5-hydroxy-4-bromoamphetamine (2M5H4BA) in blood and biological tissues of experimental rats. The rats were administered a 20 mg/kg dose of DOB·HCl by oral ingestion or subcutaneous injection. Plasma and brain, liver and lung tissues were collected at 0.5, 1, 2, 4, 8, 16, and 32 h after dosing (three animals per time point). The samples were prepared by a liquid–liquid extraction procedure and the extracts were assayed by GC–MS. After per oral application, DOB peak plasma level of 320 ng/mL was reached after one-hour post dosing as well as 2M5H4BA peak concentration of 203 ng/mL. A rapid phase of DOB absorption, 2M5H4BA formation and their tissue distribution during the first two hours after application were followed by a slow decrease rate of the elimination process until 32 h. After subcutaneous application, high plasma levels of the unchanged parent drug and relatively reduced formation of its metabolite 2M5H4BA were observed. DOB maximum plasma concentration of 1143 ng/mL was reached after one-hour post application, whereas its metabolite peak level after 8 h was 213 ng/mL. The concentration profiles of both compounds in plasma after per oral and subcutaneous administration revealed the existence of significant first pass effect after per oral administration that significantly affected DOB bioavailability. DOB tissue concentrations exceeded plasma and the highest values were found in the lungs, where drug accumulation occurred with prolonged retention till 32 h after subcutaneous dose. Although the plasma/tissue transfer was more effective for the lipophilic parent drug than for its hydroxylated metabolite 2M5H4BA, the metabolite tissue levels were significant. The hallucinogenic potential of 2M5H4BA appearing in brain remains unclear as nothing is known about its pharmacological activity at present.     

液相色谱质谱联用测定乌头碱在大鼠体内代谢产物

目的鉴定乌头碱在大鼠体内的主要代谢产物。方法灌胃给予雄性大鼠1.0mg/kg乌头碱后,收集24h尿液,固相萃取法提取,液相色谱-质谱法测定乌头碱及其代谢物。结果经与空白组对照发现给药后大鼠尿样中除乌头碱原体外还有4种代谢产物,并分别测得其准分子离子峰及其各级碎片离子。结论经与对照品比较及质谱断裂规律推断4个代谢产物分别为中乌头碱、16-O-去甲基乌头碱、16-O-去甲基中乌头碱、苯甲酰乌头碱。     

尸体脏器中安定、利眠宁及其代谢降解产物的毛细柱GC/MS鉴定

本文描述了尸体脏器中安定、利眠宁及其代谢降解产物二苯甲酮类、N-去甲安定、舒宁和脱氧利眠宁的毛细柱GC/MS鉴定方法,讨论了热解和代谢过程。     

液相色谱-串联质谱法检测生物样品中百草枯及其代谢物

目的建立生物样品中百草枯(paraquat,PQ)及其2种主要代谢物monoquat,paraquatmonopyridone(MP)的液相色谱-串联质谱(LC-MS/MS)检测方法,应用于百草枯中毒案件的法医学鉴定。方法生物样品经乙腈或甲醇沉淀蛋白,使用Agilent HILIC Plus(4.6×100mm,3.5μm)色谱柱,以0.1%甲酸水溶液～0.1%甲酸乙腈溶液(v/v)为流动相进行洗脱,在多反应监测模式下检测。结果百草枯及其代谢物在1～1000ng/mL内线性关系良好,相关系数(r)≥0.9996,最低检出限为0.34～6.00ng/mL,检测准确度为91.25%～113.44%,日内及日间精密度分别为1.51%～3.99%和1.92%～4.93%。结论本文建立的LC-MS/MS法具有灵敏度高、特异性好的特点,可应用于百草枯中毒相关案件的法医学鉴定。     

Hair and urine analysis: relative distribution of drugs and their metabolites

This work studies the distribution of cocaine and heroin metabolites in hair and urine of living polidrug abusers. Cocaine, benzoylecgonine (BEG), ecgonine methyl ester (EME), morphine, codeine and 6-monoacetylmorphine (6-MAM) were simultaneously extracted and analyzed by GC/MS in SIM mode. The results obtained show a different distribution of heroin and cocaine metabolites in urine and hair. In urine, we generally find BEG and EME for cocaine abuse, and morphine for heroin abuse. In hair, we detect cocaine and MAM as major metabolites for cocaine and heroin abuse, respectively.     

2'-氯地西泮及其代谢物的药代动力学特征的LC/MS研究

目的利用液质联用法研究2’-氯地西泮及其代谢物在大鼠体内的药代动力学规律。方法SD大鼠经灌胃给药2’-氯地西泮2.625mg/kg,给药后采集不同时间的血样。蛋白沉淀法处理血浆样品后,进样分析。结果2’-氯地西泮及其代谢物在给药后1h均达到最高血药浓度。2’-氯地西泮在大鼠体内的半衰期约为93h,在给药后144h均能检测到。3种代谢产物地洛西泮、氯甲西泮、劳拉西泮在大鼠血浆的检出时限分别24h、144h、48h。结论2’-氯地西泮在大鼠体内吸收较快,半衰期较长,原体药物和代谢物在大鼠体内的检测窗口均较长。该研究可为临床救治2’-氯地西泮中毒患者以及相关案件的侦破提供一定的实验依据。