Liu D Y, Liu Z D, Lu S L, Hider R C
Department of Pharmacy, King's College London, University of London, UK.
J Pharm Biomed Anal. 1999 Dec;21(4):759-65. doi: 10.1016/s0731-7085(99)00211-3.
Hydrophilic 3-hydroxypyridin-4-ones (HPOs), such as 1-(2'-carboxyethyl)-2-methyl-3-hydroxypyridin-4-one (CP38), 1-(3'-hydroxypropyl)-2-methyl-3-hydroxypyridin-4-one (CP41) and 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP102), are orally active iron chelators and ester prodrugs of these molecules are currently under investigation. A liquid extraction method using acetonitrile and 2-propanol (80:20 v/v) under acidic and NaCl-saturated conditions has been developed in order to efficiently extract these HPOs from various matrices. The extracted HPOs were determined using a reversed phase polymer HPLC column (PLRP-S 100 A) and the gradient ion-pair mobile phase containing tetrabutylammonium chloride (5 mM) and EDTA (0.5 mM). The extraction recovery of these chelators in phosphate buffer, rat blood and liver homogenate varied from 85 to 94%. The coefficients of variation (C.V.) for within-day determination were in the range of 1.4-3.3% at 1 mM and 2.0-4.7% at 0.1 mM. High accuracy of determination was also achieved.
亲水性3-羟基吡啶-4-酮（HPOs），如1-（2'-羧乙基）-2-甲基-3-羟基吡啶-4-酮（CP38）、1-（3'-羟丙基）-2-甲基-3-羟基吡啶-4-酮（CP41）和1-（2'-羟乙基）-2-乙基-3-羟基吡啶-4-酮（CP102），是口服活性铁螯合剂，目前正在研究这些分子的酯前药。已开发出一种在酸性和NaCl饱和条件下使用乙腈和2-丙醇（80:20 v/v）的液液萃取方法，以便从各种基质中有效萃取这些HPOs。使用反相聚合物HPLC柱（PLRP-S 100 A）和含有四丁基氯化铵（5 mM）和EDTA（0.5 mM）的梯度离子对流动相测定萃取的HPOs。这些螯合剂在磷酸盐缓冲液、大鼠血液和肝脏匀浆中的萃取回收率在85%至94%之间。日内测定的变异系数（C.V.）在1 mM时为1.4 - 3.3%，在0.1 mM时为2.0 - 4.7%。测定也具有很高的准确性。
