ULTRAFILTRATION USING THE AMICON MPS-1 FOR ASSESSING METHADONE PLASMA-PROTEIN BINDING

The percent of protein-free and protein-bound methadone were separated in methadone-spiked bank and artificial plasma, and in plasma samples taken from methadone-maintained patients using the Amicon MPS-1 ultra filtration device. Following the separation procedure, protein-bound a nd protein-free methadone were extracted from the protein-bound and fr ee fractions, and their respective concentrations were determined by g as chromatography and nitrogen-phosphorus detection. Eighty five patie nt samples from 38 men and 10 women receiving methadone maintenance we re collected and subjected to the ultrafiltration methodology. Two ind ependent procedures demonstrated that, following the ultrafiltration p rocess, no proteins were measurable in the filtrate. In addition, the ultrafiltration process was found to function independently of the con centration of methadone and the volume of sample, assuming the amount filtered never exceeded 40% of the original volume. in the patient sam ples, the %-free methadone varied sixfold across all patients. Female patients were found to have a mean +/- SD %-free methadone of 11.9 +/- 3.8% vs. 10.1 +/- 3.4% for men. Pearson correlation values suggest th at steady-state protein-free methadone levels (r = 0.521) and total me thadone levels (r = 0.491) rise as methadone dose is increased. Corres ponding to these results, free methadone levels are highly correlated with total methadone levels (Pearson r = 0.85). The Amicon MPS-1 ultra filtration device appears to be a reliable and relatively easy system to use for separating protein-free from protein-bound methadone, thoug h further study is required to clarify the clinical applications of fr ee methadone levels.