Purification Of Z-ligustilide By Supercritical Fluid Chromatography

Z-ligustilide is the main active ingredient in the herbal medicine, such asAngelica and Chuanxiong. It is a kind of anticholinergic drug and it can relieve coughand asthma. It is also a kind of effective drugs for the treatment and prevention ofcardiovascular and cerebrovascular diseases. Z-ligustilide is insoluble in water, itschemical property is very active and denature easily.Traditional purification method of Z-ligustilide which is relatively mature isethanol/acetonitrile solvent extraction-silicagel chromatography process. but there arealso shortcomings such as complex procedure, low yield, and solvent residue. So anefficient, clean Z-ligustilide purification technology is urgently needed.Supercritical fluid chromatography uses supercritical fluid as mobile phasewhich is very efficient, environmental protective. It is paid more and more attention inthe field of modern chemical separation and purification.In this paper, SFC technology was first introduced to purifing Z-ligustilide fromangelica oil. The optimal operating conditions were determined: non-polar columnZorBax SB-C18（9.4mm×250mmi.d.,5μm） was used as the stationary phase,SC-CO₂/C2H5OH was used as the mobile phase and the content of ethanol was0.69wt.%, the velocity of CO₂is10g·min^-1, temperature313.15K, pressure14MPa. Then,Z-ligustilide overloading rule in the SFC was studied, and optimal overloadingconditions were determined: overloading concentration100mg/mL and overloadingvolume20μL, Z-ligustilide product with purity of98.5%was obtained.The diffusion coefficients （D1,2） of Z-ligustilide in supercritical carbon dioxidewere studied by Taylor capillary peak broadening method at temperature305.15K to323.15K, under pressure10MPa to18MPa. The value of D1,2were in the range of（2.75⁵.55）×10^-4cm²Â·s^-1. It decreased with increasing carbon dioxide density andtemperature. It increased with the increasing content of ethanol.The method of elution by characteristic point （ECP） was used onto determineadsorption isotherm of Z-ligustilide from supercritical fluid on the ZorBax SB-C18column in the range of pressure10MPa to18MPa and temperature305.15K to323.15K. The results indicated that the loading of Z-ligustilide on the stationary phasedecreased with increasing mobile phase density and temperature.