Terauchi Y, Ishikawa S, Oida S, Nakao M, Kagemoto A, Oida T, Utsui Y, Sekine Y
Research Laboratories, Dainippon Pharmaceutical Company, Ltd., Osaka, Japan.
J Pharm Sci. 1990 May;79(5):432-6. doi: 10.1002/jps.2600790515.
A direct radioimmunoassay for the accurate determination of haloperidol in human serum has been developed. Based on recent information about the metabolism of haloperidol, a new haloperidol hapten, in which a (3-carboxypropionyl)methylamino group was attached as a bridge in the place of fluorine atom, was synthesized and coupled to bovine serum albumin through the bridge to provide a new immunogen. Guinea pigs were used for the immunization. Since the antisera obtained by the new immunogen still cross reacted greater than 10% with reduced haloperidol, the immunological tolerance to reduced haloperidol was induced by administration of a copolymer of D-glutamic acid and D-lysine linked with reduced haloperidol. This gave an antiserum in guinea pigs which was highly specific for unchanged haloperidol with negligible cross reactivity (less than or equal to 1.0%) to any haloperidol metabolites including the newly found ones. With the newly developed antiserum and [3H]haloperidol, serum haloperidol levels can be determined over the concentration range from 0.3 to 20 ng/mL, using 0.1 mL of human serum, without an extraction procedure.
已开发出一种直接放射免疫分析法，用于准确测定人血清中的氟哌啶醇。基于最近有关氟哌啶醇代谢的信息，合成了一种新的氟哌啶醇半抗原，其中(3-羧基丙酰基)甲基氨基作为桥接取代了氟原子，并通过该桥与牛血清白蛋白偶联以提供一种新的免疫原。使用豚鼠进行免疫。由于新免疫原获得的抗血清与还原型氟哌啶醇的交叉反应仍大于10%，因此通过给予与还原型氟哌啶醇连接的D-谷氨酸和D-赖氨酸共聚物诱导对还原型氟哌啶醇的免疫耐受性。这在豚鼠中产生了一种抗血清，该抗血清对未改变的氟哌啶醇具有高度特异性，对任何氟哌啶醇代谢物（包括新发现的代谢物）的交叉反应可忽略不计（小于或等于1.0%）。使用新开发的抗血清和[3H]氟哌啶醇，无需提取程序，使用0.1 mL人血清即可在0.3至20 ng/mL的浓度范围内测定血清氟哌啶醇水平。
