<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Nigakinones are the main effective compounds of <jats:italic>Picrasma quassioides</jats:italic> (D. Don) Benn and are widely used in traditional Chinese medicine, therefore a rapid and efficient separation and purification method is necessary.</jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To develop a new method based on ultrasonic microwave‐assisted extraction (UMAE) and high‐speed counter‐current chromatography (HSCCC) for the rapid separation and purification of nigakinone and methylnigakinone from <jats:italic>P. quassioides</jats:italic> (D.Don) Benn.</jats:sec><jats:sec><jats:title>Methodology</jats:title><jats:p>Response surface methodology (RSM) was used to optimise the extraction conditions of UMAE: 10.0 g of original sample was extracted with 210 mL of 90% (v/v) aqueous methanol at 60°C for 13 min, ultrasonic power was 100 W and microwave power was dynamically adjusted to the given temperature. After extraction, the extract was introduced into the HSCCC and separated with a hexane:ethyl acetate:methanol:2% acetic acid (9:11:9:11, v/v/v/v) solvent system.</jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>About 2.1 mg nigakinone with purity of 96.8% was obtained in one step within 200 min, methylnigakinone was also obtained with a purity of 75.6%. Their chemical structures were identified with ESI‐MS and <jats:sup>1</jats:sup>H‐NMR.</jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>UMAE coupled with HSCCC was found to be a promising and feasible alternative method to separate and purify alkaloids from natural herbs such as <jats:italic>P. quassiodes</jats:italic>. Copyright © 2012 John Wiley & Sons, Ltd.</jats:sec>