目的 測(cè)定蒿甲醚在正辛醇-水/緩沖體系中的表觀油水分配系數(shù)（lgP）及其在常用的注射用油、乳化劑及助乳化劑等不同介質(zhì)中的平衡溶解度。方法 使用搖瓶法測(cè)定蒿甲醚在正辛醇-水中的lgP；采用高效液相色譜法（HPLC）測(cè)定蒿甲醚在各種介質(zhì)中的濃度。結(jié)果 在37 ℃下，蒿甲醚在水及pH 5.0、6.8、7.4、8.0的磷酸鹽緩沖液中的lgP分別為2.2、1.6、1.5、2.6、2.2。在37 ℃時(shí)，蒿甲醚在注射用油中鏈甘油三酯（MCT)、橄欖油、大豆油、蓖麻油及肉豆蔻酸異丙酯（IPM）中的平衡溶解度分別為306.9、246.6、222.8、265.0、273.3 mg/mL。在乳化劑（6 mg/mL膠束溶液）泊洛沙姆188（F68）、壬基酚聚氧乙烯醚（OP乳化劑）、聚山梨酯80、大豆卵磷脂、聚氧乙烯氫化蓖麻油（RH40）中的平衡溶解度分別為0.1、1.4、0.5、0.6、0.6 mg/mL。在無水乙醇、1, 2-丙二醇、丙三醇、異丙醇、正丁醇中的平衡溶解度分別為177.3、37.0、3.4、204.1、303.1 mg/mL。結(jié)論 蒿甲醚表觀油水分配系數(shù)隨水相pH不同而不同；蒿甲醚在注射用油MCT、OP乳化劑、助乳化劑正丁醇中的溶解度較大。

Objective To determine the apparent partition coefficients (lgP) of artemether in octanol-water/buffer systems as well as its equilibrium solubility in various media, such as oil for injection, surfactants, and co-surfactants. Methods Waving bottle method was adopted to determine the lgP of artemether in octanol-water/buffer. High performance liquid chromatography (HPLC) was used to determine the concentration of artemether in different media. Results lgP values of artemether in octanol-water or buffer solutions (pH 5.0, 6.8, 7.4, and 8.0) were 2.2, 1.6, 1.5, 2.6, and 2.2, respectively. The equilibrium solubility of artemether in injection oil media-chain triglycerides (MCT), olive oil, soybean oil, castor oil, and isopropyl myristate (IPM) at 37 ℃ was 306.9, 246.6, 222.8, 265.0, and 273.3 mg/mL, respectively. The equilibrium solubility of artemether in surfactant (6 mg/mL micellar solution), such as Poloxamer 188 (F68), OP emulsifier (OP), polysorbate 80, soybean lecithin, and cremophor-RH40 (RH40) was 0.1, 1.4, 0.5, 0.6, and 0.6 mg/mL, respectively. The equilibrium solubility of artermether in cosurfactants ethanol, propylene glycol, glycerin, isopropyl alcohol, and n-butanol was 177.3, 37.0, 3.4, 204.1, and 303.1 mg/mL, respectively. Conclusion The lgP of artemether is different in buffer with difference of pH values. Artemether has a higher solubility in MCT, surfactant OP, and cosurfactant n-butanol.

國家自然科學(xué)基金資助項(xiàng)目（30973589）；山西省回國留學(xué)人員科研項(xiàng)目（2009-47）