Jennison T A, Finkle B S, Chinn D M, Crouch D J
J Chromatogr Sci. 1979 Feb;17(2):64-74. doi: 10.1093/chromsci/17.2.64.
1-alpha-acetylmethadol (LAAM) is a new drug under development for the treatment of heroin dependence. A new analytical method applicable to the accurate biodispositional study of the drug and its metabolities is described and critically discussed in this report. The procedure involves sample preparation and direct organic solvent extraction using eta-butyl chloride, amide derivatization by molecular rearrangement, and gas chromatography-chemical ionization mass spectrometry-selected ion monitoring, with methane as the carrier and ammonia as reagent gases. Deuterated (d3 stable isotopes of LAAM and its metabolites are used as internal standards. The method is free from qualitative interferences and has quantitative sensitivity to 5 ng/ml for 2.0 ml samples with 10-15% accuracy and precision in the range 5-100 ng/ml; and 2-5% at concentrations up to 750 ng/ml. Specimens of plasma, whole blood, urine, bile, brain, liver, and other visceral samples have been successfully analyzed, as well as in vitro preparations such as hepatic microsomes. By appropriate data processing, the method lends itself to routine analysis and high volume work; even manually the method is capable of at least 50 samples per week. A simplified procedure for the analysis of LAAM and its metabolites in urine only is also presented and discuet up and use the methods.
1-α-乙酰美沙多（LAAM）是一种正在研发用于治疗海洛因依赖的新药。本报告描述并批判性地讨论了一种适用于该药物及其代谢物准确生物处置研究的新分析方法。该程序包括样品制备、使用氯丁烷进行直接有机溶剂萃取、通过分子重排进行酰胺衍生化以及气相色谱-化学电离质谱-选择离子监测，以甲烷作为载气，氨作为反应气。氘代（d3）的LAAM及其代谢物的稳定同位素用作内标。该方法无定性干扰，对2.0 ml样品中5 ng/ml的浓度具有定量灵敏度，在5 - 100 ng/ml范围内准确度和精密度为10 - 15%；在浓度高达750 ng/ml时为2 - 5%。血浆、全血、尿液、胆汁、脑、肝和其他内脏样品以及肝微粒体等体外制剂已成功分析。通过适当的数据处理，该方法适用于常规分析和大量工作；即使手动操作，该方法每周至少能够处理50个样品。还介绍了仅用于分析尿液中LAAM及其代谢物的简化程序，并讨论了该方法的使用。
