HPLC法测定胡黄连苷Ⅰ的表观油水分配系数和平衡溶解度

目的：测定胡黄连苷Ⅰ在不同pH水溶液中的平衡溶解度及其在正辛醇-水系统中的油水分配系数。方法：采用摇瓶-高效液相色谱法测定胡黄连苷Ⅰ在水和不同pH缓冲液介质中的平衡溶解度及在正辛醇-水/缓冲液中的油水分配系数。色谱条件：采用Agilent Zorbax SB-Aq色谱柱（4.6mm×250 mm，5 μm），流动相为乙腈-0.125%磷酸水溶液（22：78），流速1.0 mL· min^-1，检测波长275 nm，柱温30℃。结果：在37℃下，胡黄连苷Ⅰ在pH为1.2、2.0、5.0、6.8和7.4的缓冲液以及水中，平衡溶解度分别为42.32、39.76、46.85、52.69、55.00和75.23 g·L^-1，表观油水分配系数平均值分别为0.265、0.253、-0.010、0.171、0.112和0.073。结论：本文建立的测定胡黄连苷Ⅰ的摇瓶-HPLC法简单可行。胡黄连苷Ⅰ是高溶解性及低渗透性的药物，水溶性好，脂溶性差，且pH能影响平衡溶解度和表观油水分配系数。

Objective:To determine the equilibrium solubility of picrosideⅠ in water with different pH and the oil-water partition coefficient in n-octanol-water soulution.Methods:The concentration of picrosideⅠin solutions at different pH values and the partition coefficients in n-octanol-water and n-octanol-buffer solution systems were measured by shaking flask-HPLC method.Separation was performed on an Agilent Zorbax SB-Aq column (4.6 mm×250 mm, 5 μm), the mobile phase consisted of acetonitrile-0.125% phosphoric acid (22:78) at a flow rate of 1.0 mL·min^-1.The detective wavelength was 275 nm and the column temperature was 30℃.Results:At 37℃, the equilibrium solubilities of picrosideⅠin buffer solutions (at pH 1.2, 2.0, 5.0, 6.8 and 7.4) and in water, were 42.32, 39.76, 46.85, 52.69, 55.00 and 75.23 g·L^-1, respectively.And the oil-water partition coefficients were 0.265, 0.253, -0.010, 0.253, 0.112 and 0.073, respectively.Conclusion:The shaking flask-HPLC method is simple and rapid to determine the oil-water partition coefficient of picrosideⅠ.PicrosideⅠ has characteristics of high solubility, low permeability, good water solubility and poor lipid solubility.The equilibrium solubility and apparent oil/water partition coefficient of picroside Ⅰ are greatly influenced by pH value.

[1] 黄开毅,何乐,王大成,等.西藏胡黄连的化学成分[J].中国药学杂志,2008,43(18):1382 HUANG KY,HE L,WANG DC et al.Chemical constituents of Picrorhiza scrophulariiflora[J].Chin Pharm J,2008,43(18):1382
[2] 金诚,吴飞,郑晓,等.胡黄连的化学成分、质量分析和药理作用研究进展[J].中国新药杂志,2019,28(3):292 JIN C,WU F,ZHENG X,et al.Research progress on the chemical composition,analytical method and pharmacological action of Rhizoma Picrorhizae[J].Chin J New Drugs,2019,28(3):292
[3] 龚苏晓.胡黄连中增强神经生长因子作用的化合物[J].国际中医中药杂志,2001,23(6):343 GONG SX.Compounds that enhance the role of nerve growth factors in Picrorhiza scrophulariiflora[J].Int J Tradit Chin Med,2001,23(6):343
[4] KAPADIA GJ,SHARMA SC,TOKUDA H,et al.Inhibitory effect of iridoids on Epstein-Barr virus activation by a short-term in vitro assay for anti-tumor promoters[J].Cancer Lett,1996,102(1-2):223
[5] 中华人民共和国药典2015年版.四部[S].2015:324 ChP 2015.Vol Ⅳ[S].2015:324
[6] PARDEIKE J,MULLER RH.Nanosuspensions:a promising formulation for the new phospholipase A2 inhibitor PX-18[J].Int J Pharm,2010,391(1/2):322
[7] 钱桂英,狄留庆,单进军,等.祖师麻总香豆素物理化学常数的测定[J].中国中医药信息杂志,2006,13(10):521 QIAN GY,DI LQ,SHAN JJ,et al.Determination of the physical chemistry constants of total cumarin[J].Chin J Inf Tradit Chin Med,2006,13(10):521
[8] 史小玉,张广彬,魏赛丽.HPLC-荧光法测定土大黄苷平衡溶解度和油水分配系数[J].西安交通大学学报,2013,34(5):682 SHI XY,ZHANG GB,WEI SL.Determination of the equilibrium solubility of rhaponticin and oil-water apparent patition coefficients using HPLC-fluorometric method[J].J Xi'an Jiaotong Univ Med Sci,2013,34(5):682
[9] 朱伊婷,陈英杰,夏媛媛,等.甲磺酸普依司他油水分配系数的测定[J].广东化工,2018,45(10):36 ZHU YT,CHEN YJ,XIA YY,et al.Determination of the partition coefficient for purinostat mesylate[J].Guangdong Chem Ind,2018,45(10):36
[10] 姚媛,廖琼峰,曾丽英,等.穿心莲内酯和脱水穿心莲内酯表观油水分配系数的测定及pH值对其的影响[J].中药材,2009,32(10):1610 YAO Y,LIAO QF,ZENG LY,et al.Determination of apparent oil-water partition coeficient of andrographolide and dehydroandrographolide and effect of pH on them[J].J Chin Med Mater,2009,32(10):1610
[11] DRESSMAN JB,AMIDON GL,REPPAS C,et al.Dissolution testing as a prognostic tool for oral drug absorption:immediate release dosage forms[J].Pharm Res,1998,15(1):11
[12] 熊耀坤,梁爽,杜焰,等.HPLC法测定洋川芎内酯Ⅰ的平衡溶解度和表观油水分配系数[J].药物分析杂志,2012,32(9):1644 XIONG YK,LIANG S,DU Y,et al.HPLC determination of equilibrium solubility and apparent oil/water partition coefficient of senkyunolide Ⅰ[J].Chin J Pharm Anal,2012,32(9):1644
[13] 高宏伟,匡海学,阎雪莹.胡黄连苦苷Ⅰ大鼠在体肠吸收动力学研究[J].中医药信息,2011,28(4):7 GAO HW,KUANG HX,YAN XY.The absorption kinetics of picroside Ⅰ in the body intestinal of rats[J].Inf Tradit Chin Med,2011,28(4):7
[14] 张卫平,孙小成,王静,等.胡黄连苷Ⅰ和胡黄连苷Ⅱ在大鼠体内的药物动力学[J].沈阳药科大学学报,2013,30(9):724 ZHANG WP,SUN XC,WANG J,et al.The pharmacokinetics of picroside Ⅰ and picrosideⅡ in rats[J].J Shenyang Pharm Univ,2013,30(9):724
[15] 梁晓东,张丽,贾志丹,等.注射用胡黄连总苷对α-萘异硫氰酸酯诱发小鼠胆汁淤积性黄疸的保肝退黄作用[J].中国药物警戒,2014,11(8):453 LIANG XD,ZHANG L,JIA ZD,et al.Effects of total glucoside of on intrahepatic cholestasis in mice induced by α-naphthylisothiocyanate[J].Chin J Pharmacovigil,2014,11(8):453
[16] 王淑娟,贾志丹,魏怀玲,等.注射用胡黄连总苷对ConA引起小鼠急性免疫性肝损伤的保护作用研究[J].中国药物警戒,2013,10(12):705 WANG SJ,JIA ZD,WEI HL,et al.Protective effect of total glucoside of Picrorhiza scrophulariflora for injection on concanvalin A-induced liver injury in mice[J].Chin J Pharmacovigil,2013,10(12):705
[17] 李静姿,田硕涵,赵侠,等.注射用胡黄连总苷在健康人体的药动学[J].中国新药杂志,2014,23(21):2526 LI JZ,TIAN SH,ZHAO X,et al.The pharmacokinetics of total glucosides of Picrorhiza scrophulariiflora for injection in healthy subjects[J].Chin J New Drugs,2014,23(21):2526
[18] 周颖,赵侠,向倩,等.注射用胡黄连总苷耐受性研究[J].中国新药杂志,2008,17(17):1529 ZHOU Y,ZHAO X,XIANG Q,et al.Tolerance of total glucosides of Picrorhiza scrophulariiflora for injection in Chinese healthy volunteers[J].Chin J New Drugs,2008,17(17):1529