HPLC法测定胡黄连苷Ⅰ的表观油水分配系数和平衡溶解度
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摘要
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,5μm),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 picroside Ⅰ in water with different pH and the oil-water partition coefficient in n-octanol-water soulution.Methods:The concentration of picroside Ⅰ in 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 picroside 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 picroside Ⅰ.Picroside Ⅰ 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.
Objective:To determine the equilibrium solubility of picroside Ⅰ in water with different pH and the oil-water partition coefficient in n-octanol-water soulution.Methods:The concentration of picroside Ⅰ in 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 picroside 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 picroside Ⅰ.Picroside Ⅰ 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.
引文
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[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):724ZHANG WP,SUN XC,WANG J,et al.The pharmacokinetics of picrosideⅠand picrosideⅡin 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):453LIANG XD,ZHANG L,JIA ZD,et al.Effects of total glucoside of on intrahepatic cholestasis in mice induced byα-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):705WANG 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):2526LI 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):1529ZHOU 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
[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):292JIN 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):343GONG 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].2015:324ChP 2015.VolⅣ[S].2015:324
[6]PARDEIKE J,MULLER RH.Nanosuspensions:a promising formulation for the new phospholipase A2 inhibitor PX-18[J].Int JPharm,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):521QIAN 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):682SHI 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):36ZHU 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):1610YAO Y,LIAO QF,ZENG LY,et al.Determination of apparent oilwater 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):1644XIONG YK,LIANG S,DU Y,et al.HPLC determination of equilibrium solubility and apparent oil/water partition coefficient of senkyunolideⅠ[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):7GAO HW,KUANG HX,YAN XY.The absorption kinetics of picrosideⅠin 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):724ZHANG WP,SUN XC,WANG J,et al.The pharmacokinetics of picrosideⅠand picrosideⅡin 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):453LIANG XD,ZHANG L,JIA ZD,et al.Effects of total glucoside of on intrahepatic cholestasis in mice induced byα-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):705WANG 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):2526LI 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):1529ZHOU 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
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