In order to support studies on various medication protocols for the treatment of cocaine abuse, an accurate, precise, and sensitive (2.5 to 750 ng/mL) liquid chromatography-tandem mass spectrometry assay was developed to determine cocaine and benzoylecgonine in human plasma. Cocaine-d3 and benzoylecgonine-d3 were added as internal standards and samples were subjected to solid-phase extraction. Cocaine recovery was 94.4% and benzoylecgonine was 80.3% at 2.5 ng/mL. The selected reaction monitoring of parent ions at m/z 304 and 290 resulted in strong fragments at m/z 182 and 168 for cocaine and benzoylecgonine, respectively. The method was fully validated. The mean measured concentration at the 2.5 ng/mL, the lower limit of quantitation, was within 10.8% of the target and the precision determined at the low (5 ng/mL), medium (50 ng/mL), and high (650 ng/mL) quality controls ranged from 0.9 to 6.2 %CV. Cocaine and benzoylecgonine concentrations in plasma treated with 1% NaF showed changes of less than 10% when maintained at room temperature for up to 7 h and no significant changes when subjected to three freeze-thaw cycles. The concentrations of cocaine and benzoylecgonine remained stable in plasma samples stored at -20 degrees C for up to 11 months. Methanolic stock solutions of both analytes are stable, staying within 2% of the freshly prepared stock solutions, when stored at -20 degrees C for up to 235 days. Both extracted analytes reconstituted in methanolic solutions are stable for up to seven days whether stored at -20 degrees C or at room temperature on the autosampler. The method is rugged, rapid, and robust and has been applied to the batch analysis of more than 700 samples during pharmacokinetic profiling to assess potential interactions between intravenous (i.v.) cocaine challenge and treament medications. Results from three of these subjects receiving 40 mg (i.v.) cocaine demonstrate the utility of the method.

译文

为了支持对治疗可卡因滥用的各种药物方案的研究,开发了一种准确,精确和灵敏 (2.5 750 ng/mL) 的液相色谱-串联质谱测定法,以测定人血浆中的可卡因和苯甲酰芽子碱。加入Cocaine-d3和benzoylecgonine-d3作为内标物,样品进行固相萃取。94.4% 可卡因回收,并以2.5 ng/mL 80.3% 苯甲酰腺嘧啶。在m/z 304和290对母体离子的选定反应监测分别导致可卡因和苯甲酰芽子碱在m/z 182和168处的强片段。该方法得到了充分验证。在2.5 ng/mL (定量下限) 下的平均测量浓度在目标的10.8% 内,并且在低 (5 ng/mL),培养基 (50 ng/mL) 下确定的精密度,高 (650 ng/mL) 质量控制范围为0.9至6.2% CV。当在室温下保持长达7小时时,用1% NaF处理的血浆中的可卡因和苯甲酰芽子碱浓度显示出小于10% 的变化,而当经历三个冻融循环时,没有显着变化。在-20摄氏度下储存的血浆样品中,可卡因和苯甲酰腺嘧啶的浓度保持稳定长达11个月。当在-20摄氏度下储存长达235天时,两种分析物的甲醇储备溶液都是稳定的,保持在新鲜制备的储备溶液的2% 内。在甲醇溶液中重构的两种提取的分析物无论在-20摄氏度下还是在自动进样器上的室温下均稳定长达7天。该方法是坚固的、快速的和稳健的,并且已经应用于在药代动力学分析期间对超过700个样品进行分批分析,以评估静脉内 (静脉内) 可卡因攻击和治疗药物之间的潜在相互作用。其中三名接受40 mg (i.v.) 可卡因的受试者的结果证明了该方法的实用性。

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