SENSITIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY WITH ULTRAVIOLET DETECTION OF METHADONE ENANTIOMERS IN PLASMA

Methadone is being prescribed increasingly as an analgesic in palliati ve medicine. R-Methadone has been shown to be responsible for most of the pharmacological activity of this drug. Despite this, in most count ries it is administered as the racemate. Few assay methods for the ena ntiomers are available; even fewer can determine accurately the low co ncentrations of enantiomers required to undertake pharmacokinetic stud ies in patients taking the drug in analgesic doses. We present here an HPLC method used to determine concentrations of the specific enantiom ers of methadone as low as 5.0 ng/ml with adequate precision and accur acy. The mean RIS 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 pa tient, concentrations of the enantiomers ranged between 5.8 and 25.9 n g/ml. Tricyclic antidepressants did not interfere with the assay but d extropropoxyphene did. Its presence could be detected by dual waveleng th monitoring.