Kristensen K, Angelo H R
Royal Danish School of Pharmacy, Copenhagen.
Chirality. 1992;4(4):263-7. doi: 10.1002/chir.530040410.
rac-Methadone is used clinically for the chronic maintenance treatment of heroin addiction and for the relief of pain. As the pharmacological activity of methadone is due primarily to the (-)-(R)-enantiomer, stereospecific measurements of methadone serum concentrations in methadone-treated patients are expected to be more relevant for clinical studies than earlier described total drug measurements. This study describes a stereospecific gas chromatographic (GC) method for the determination of methadone in serum. The extracted methadone was derivatizised with (-)-menthyl chloroformate. The diastereometric derivatives were analysed by GC on a capillary column and detected with a nitrogen-phosphorus detector. The resolution factor obtained for the methadone enantiomers was 1.1 with a relatively short time of analysis (30 min). By analysing the pure (-)-(R)-enantiomer, no racemization was seen during the analysis. The lower limit of quantitation was 75 nmol/l for each enantiomer. Measurements of the ratio between (-)-(R)- and (+)-(S)-methadone concentrations in serum from five methadone-treated patients showed interindividual differences (range 0.5-1.1). The patient results correlated well with those from another GC method measuring total methadone.
消旋美沙酮在临床上用于海洛因成瘾的慢性维持治疗及缓解疼痛。由于美沙酮的药理活性主要归因于(-)-(R)-对映体，因此在美沙酮治疗患者中对美沙酮血清浓度进行立体特异性测量，相较于之前所描述的总药物测量，预计对临床研究更具相关性。本研究描述了一种用于测定血清中美沙酮的立体特异性气相色谱(GC)方法。提取的美沙酮用(-)-氯甲酸薄荷酯进行衍生化。通过气相色谱在毛细管柱上分析非对映体衍生物，并用氮磷检测器进行检测。美沙酮对映体获得的分离度因子为1.1，分析时间相对较短(30分钟)。通过分析纯(-)-(R)-对映体，在分析过程中未观察到消旋化现象。每种对映体的定量下限为75 nmol/l。对五名接受美沙酮治疗患者血清中(-)-(R)-美沙酮与(+)-(S)-美沙酮浓度之比的测量显示个体间存在差异(范围为0.5 - 1.1)。患者的结果与另一种测量美沙酮总量的气相色谱方法的结果相关性良好。
