多沙唑嗪对映体在大鼠血浆中的测定及手性转化研究  

Determination of doxazosin enantiomers in rat plasma and investigation of their chiral inversion

作　　者：甄亚钦[1] 孔德志[1] 李清[1] 赵静[1] 任雷鸣[1] 

机构地区：[1]河北医科大学中西医结合研究所,河北石家庄050017

出　　处：《药学学报》2013年第6期901-905,共5页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划(973计划)资助项目(2012CB518601);国家科技部"重大新药创制"科技重大专项资助项目(2011ZX09102-011-04);国家自然科学基金资助项目(30940088)

摘　　要：建立大鼠血浆中多沙唑嗪对映体的高效液相色谱荧光测定方法,并研究多沙唑嗪对映体在体内外的手性转化情况。采用卵黏蛋白手性色谱柱,柱温30℃;荧光检测激发波长和发射波长分别为255和385nm;乙腈?磷酸盐缓冲液(15∶85,v/v)为流动相,流速0.8mL·min?1;内标为哌唑嗪。体外研究:将分别加入左旋多沙唑嗪、右旋多沙唑嗪的大鼠血浆于37℃水浴温育2天、5天、10天后测定;体内研究:SD大鼠连续口服左旋多沙唑嗪、右旋多沙唑嗪溶液1个月,于最后一次给药8h后腹主动脉取血测定。结果表明,多沙唑嗪两种对映体检测浓度在4～2000ng·mL?1内线性关系良好,左旋多沙唑嗪平均回收率为99.5%,RSD为3.6%;右旋多沙唑嗪平均回收率为99.3%,RSD为4.3%。多沙唑嗪对映体与大鼠血浆的体外共同温育实验中,未观察到转化现象;大鼠连续口服左旋或右旋多沙唑嗪1个月,在血浆中也未观察到手性转化现象。该分析方法选择性强、准确度高、重现性好,适于多沙唑嗪对映体在大鼠血浆中的测定研究。体内外研究表明多沙唑嗪对映体不易发生相互转化。The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 ℃. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile （85 ： 15, v/v） at a flow rate of 0.8 mL.min-1 was done. The fluorescence detection was set at λEx=255 nm and 2,Em=385 nm. Prazosin was used as the internal standard. （-） Doxazosin or （＋） doxazosin added into rat plasma in vitro was determined after incubating in 37 ℃ water bath for 2, 5 and 10 days. （-） Doxazosin or （＋） doxazosin was administered orally to the rats for one months. Plasma samples were taken at 8 h after the last administration. A good linear relationship was achieved when the concentration of doxazosin enantiomers was within the range of 4 - 2 000 ng＇mL-1. The average recovery for （-） doxazosin was 99.5% with RSD 3.6%, and for （＋） doxazosin was 99.3% with RSD 4.3%. Chiral inversion was observed neither in vitro nor in vivo studies. The method is selective, accurate and reproducible, which is suitable for the detection of doxazosin enantiomers in rat plasma. The in vitro and in vivo studies indicate that chiral inversion occurs uneasily between （-） doxazosin and （＋） doxazosin in the rat.

关 键 词：多沙唑嗪 对映体 高效液相色谱 手性转化 

分 类 号：R917[医药卫生—药物分析学]