Norris R L, Ravenscroft P J, Pond S M
Department of Clinical Pharmacology, Princess Alexandra Hospital, Woolloongabba, Qld, Australia.
J Chromatogr B Biomed Appl. 1994 Nov 18;661(2):346-50. doi: 10.1016/0378-4347(94)00341-6.
Methadone is being prescribed increasingly as an analgesic in palliative medicine. R-Methadone has been shown to be responsible for most of the pharmacological activity of this drug. Despite that in most countries it is administered as the racemate. Few assay methods for the enantiomers are available; e en fewer can determine accurately the low concentrations of enantiomers required to undertake pharmacokinetic studies in patients taking the drug in analgesic doses. We present here an HPLC method used to determine concentrations of the specific enantiomers of methadone as low as 5.0 ng/ml with adequate precision and accuracy. The mean R/S ratio of the plasma concentrations was 0.80 +/- 0.05 (n = 3 samples) in one patient taking 25-27.5 mg daily and 1.21 +/- 0.12 (n = 6 samples) in another taking 10-20 mg daily. In the second patient, concentrations of the enantiomers ranged between 5.8 and 25.9 ng/ml. Tricyclic antidepressants did not interfere with the assay but dextropropoxyphene did. Its presence could be detected by dual wavelength monitoring.
美沙酮在姑息治疗中作为镇痛药的处方量日益增加。已证明R-美沙酮是该药物大部分药理活性的原因。尽管在大多数国家它是以消旋体形式给药。但针对对映体的分析方法很少；能够准确测定服用镇痛剂量药物的患者进行药代动力学研究所需的低浓度对映体的方法更少。我们在此介绍一种高效液相色谱法，该方法能够以足够的精密度和准确度测定低至5.0 ng/ml的美沙酮特定对映体浓度。一名每天服用25 - 27.5 mg的患者血浆浓度的平均R/S比为0.80 +/- 0.05（n = 3个样本），另一名每天服用10 - 20 mg的患者血浆浓度的平均R/S比为1.21 +/- 0.12（n = 6个样本）。在第二名患者中，对映体浓度在5.8至25.9 ng/ml之间。三环类抗抑郁药不干扰该测定，但右丙氧芬会干扰。其存在可通过双波长监测检测到。
