A new, green, and without solvent extraction method and chiral separation system effective in separation of racemic methadone is presented. We have used sheep leather as the membrane in enantioselective extraction for chiral separation of methadone. In this work, chiral (2-hydroxypropyl)-β-cyclodextrin (OHP-β-CD) was used as a versatile chiral selector. The influences of various conditions on the separation performance were studied. Results showed, the selectivity in one separation step is related to the thickness of leather, chiral selector concentration, pH and temperature of sample solution. At optimum conditions (0.3 mm for thickness of leather, 5 g/L of chiral selector concentration, pH of sample equal to 4.3 and temperature equal to 20 °C), the distribution ratio of R- and S-methadone was 19.4 and 1.6, respectively, and the enantioselectivity value of 12.1 was found at best condition.
