Fluphenazine-4-chlorophenoxy-isobutyrate ester, a new phenothiazine derivative was synthesized in the Institute for Drug Research Budapest. Radioimmunoassay was developed for the therapeutic monitoring of the drug level after intramuscular depot injection. The fluphenazine hapten was coupled to BSA by mixed-anhydride method. Antisera were produced to this conjugation in New-Zealand white rabbits and were tested for the antibody-titer. The specificity was tested by the cross-reaction with phenothiazine-analogues and other psychotropics. Strong cross-reaction was found with compounds possessing piperazine in side chain (trifluoperazine, perphenazine), but other psychotropic drugs did not react. Tritium-labelled trifluoperazine (spec. activity: 3.5 TBq/mmol) was used as a tracer in the radioimmunoassay. The detection limit was 75 pg with a CV of < 5% in 50 microliters plasma sample (equivalent to 1.5 ng/ml concentration) and a standard curve in the 3 ng/ml-50 ng/ml GYKI-22441 concentration range showed a CV of < 10%. Preliminary pharmacokinetic study was performed in Beagle dogs after intramuscular depot injection with GYKI-22441 in sesame oil in a dose of 0.1 mg/kg. The GYKI-22441 concentration of the plasma samples were measured by the RIA method during a 28-day interval after the treatment and was evaluated by the MultiCalc Immunoassay Data Management program (Pharmacia).

中文翻译：

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一种新的吩噻嗪衍生物的放射免疫分析及其应用。

布达佩斯药物研究所合成了一种新的吩噻嗪衍生物氟吩嗪-4-氯苯氧基异丁酸酯。开发了放射免疫测定法，用于肌肉注射储库后的药物水平的治疗性监测。通过混合酸酐法将氟奋乃静半抗原与BSA偶联。在新西兰白兔中产生针对这种缀合的抗血清，并测试其抗体滴度。通过与吩噻嗪类似物和其他精神药物的交叉反应来检验特异性。发现在侧链具有哌嗪的化合物（三氟拉嗪，奋乃静）具有很强的交叉反应，但其他精神药物未反应。the标记的三氟拉嗪（比活度：3.5 TBq / mmol）在放射免疫分析中用作示踪剂。检测限为75 pg，CV < 在50微升血浆样品中的5％（相当于1.5 ng / ml浓度）和在3 ng / ml-50 ng / ml GYKI-22441浓度范围内的标准曲线显示CV <10％。在比格犬中以0.1 mg / kg的剂量在肌油中注射GYKI-22441的芝麻油进行了初步的药代动力学研究。在治疗后的28天间隔内，通过RIA方法测量血浆样品的GYKI-22441浓度，并通过MultiCalc免疫测定数据管理程序（Pharmacia）进行评估。在比格犬中以0.1 mg / kg的剂量在肌油中注射GYKI-22441的芝麻油进行了初步的药代动力学研究。在治疗后的28天间隔内，通过RIA方法测量血浆样品的GYKI-22441浓度，并通过MultiCalc免疫测定数据管理程序（Pharmacia）进行评估。在比格犬中以0.1 mg / kg的剂量在肌油中注射GYKI-22441的芝麻油进行了初步的药代动力学研究。在治疗后的28天间隔内，通过RIA方法测量血浆样品的GYKI-22441浓度，并通过MultiCalc免疫测定数据管理程序（Pharmacia）进行评估。