PHARMACOKINETICS OF MORPHINE AND ITS SURROGATES .2. METHODS OF SEPARATION OF STABILIZED HEROIN AND ITS METABOLITES FROM HYDROLYZING BIOLOGICAL-FLUIDS AND APPLICATIONS TO PROTEIN-BINDING AND RED BLOOD-CELL PARTITION STUDIES
PHARMACOKINETICS OF MORPHINE AND ITS SURROGATES .2. METHODS OF SEPARATION OF STABILIZED HEROIN AND ITS METABOLITES FROM HYDROLYZING BIOLOGICAL-FLUIDS AND APPLICATIONS TO PROTEIN-BINDING AND RED BLOOD-CELL PARTITION STUDIES
复制标题
DOI：
10.1002/jps.2600680111
复制
发表时间：
1979-01-01
影响因子：
3.8
通讯作者：
GURKAN, T
中科院分区：
文献类型：
--
作者：
GARRETT, ER;GURKAN, T
通过10 mg氟化钠/ml（t1/2 = 40 min）和35 μ g焦磷酸四乙酯/ml（t1/2 = 415 min）抑制新鲜狗血浆和血液中海洛因的自发水解（t1/2 [半衰期] = 8 min）。焦磷酸四乙酯是首选的抑制剂，对海洛因具有与磷酸盐缓冲液相同的稳定性。老化血浆失去其酶促效率。脑脊液中的海洛因水解速率与缓冲液中的相似。改进的提取程序开发的酶抑制血浆在pH 4.5有很高的提取效率（86-100%），并允许未降解的海洛因从其代谢产物的分离。从酶抑制血浆中分离海洛因和代谢物的影响，所描述的高压液相色谱系统，并从TLC洗脱相关的开发斑点。TLC回收率为81 ± 10%。海洛因为1%，82 .+-. 1%吗啡。海洛因具有显著的蛋白结合，其中40%未结合到超滤膜的蛋白结合到狗血浆蛋白。表观分配系数为1.4 ±。0.2红细胞和血浆H2O之间的比例为0.8 ± 0.001。0.1红细胞和狗血浆的区别
The inhibition of the spontaneous hydrolysis of heroin in fresh dog plasma and blood (t1/2 [half-life] = 8 min) is effected by 10 mg of sodium fluoride/ml (t1/2 = 40 min) and 35 .mu.g of tetraethyl pyrophosphate/ml (t1/2 = 415 min). Tetraethyl pyrophosphate is the inhibitor of choice and gives the same stability for heroin as in phosphate buffer. Aged plasma loses its enzymatic efficiency. Heroin in CSF hydrolyzes at rates similar to those in buffer. Modified extraction procedures developed for enzyme-inhibited plasma at pH 4.5 have high extraction efficiencies (86-100%) and permit isolation of undegraded heroin from its metabolites. Separations of heroin and metabolites from enzyme-inhibited plasma were effected by described high-pressure liquid chromatographic systems and from TLC with elution of pertinent developed spots. Efficiencies of these TLC recoveries were 81 .+-. 1% for heroin and 82 .+-. 1% for morphine. Heroin has significant protein binding where 40% of that not bound to an ultrafiltration membrane is bound to dog plasma proteins. The apparent partition coefficient is 1.4 .+-. 0.2 between red blood cells and plasma H2O, and it is 0.8 .+-. 0.1 between red blood cells and dog plasma.