Tetrandrine (TET) and fangchinoline (FAN) are basic and highly hydrophobic drugs with log P＞5.7. In this work, a simple, inexpensive and efficient liquid-phase microextraction (LPME) technology combined with high-performance liquid chromatography (HPLC) was developed for the simultaneous analysis of tetrandrine and fangchinoline in plasma samples. Tetrahydropalmatine was used as internal standard. Several parameters influencing the efficiency of LPME were investigated and optimized including organic solvent, stirring rate, extraction time, salt concentration, organic modifier and pH. Under the optimal conditions, extraction recoveries from plasma samples were 46% for tetrandrine and 50% for fangchinoline, corresponding to the drugs enriched by a factor of 23 and 25 by LPME, respectively. Excellent sample clean-up was observed and good linearities with correlation coefficients (r) of 0.9979 (FAN) and 0.9995 (TET) were obtained in the range of 15-1000 ngmL−1. The limits of detection (LOD, S/N=3) were 3.0ngmL−1 for FAN and 2.0ngmL−1 for TET.