蛋白质对测定血清中抗精神病类药物的影响及消除

Effect of Protein on the Detection of Antipsychotic Drug Residues in Human Serum and Its Elimination

以人血清白蛋白(HSA)为模型,研究了蛋白质对测定血清样品中抗精神病类药物(APDs:安定、盐酸氯丙嗪及奋乃静)的影响。以分子荧光光谱法详细研究了抗精神病类药物与HSA的相互作用,以瑞利散射光谱研究了不同浓度乙醇对蛋白质变性的影响。研究表明:药物与HSA存在牢固结合作用,体积分数为80%的乙醇水溶液为萃取液提取血清样品中的APDs时,可以使血清中蛋白质缓慢变性,充分释放与其结合的药物。乙醇水溶液萃取液中加入K2HPO4无机盐后可形成双水相体系,APDs可进入双水相上相实现药物的均相高效萃取,上相经过滤后可直接进行高效液相色谱(HPLC)检测。该方法用于人血清中三种抗精神病类药物的检测,检出限为18.8～38.4ng·mL-1,回收率为94.2%～98.7%。方法步骤简单,绿色环保,准确。

Using pure human serum albumin（HSA）as the model protein,the effects of protein on the extraction of antipsychotic drugs（APDs：diazepam,chlorpromazine hydrochloride,and perphenazine）in human serum sample were studied.The present paper investigated the interaction between APDs and HSA by fluorescence spectrometry in detail.The influences of different ethanol concentration solution on protein denaturation were studied by Rayleigh scattering.The results showed that APDs strongly bound with HSA.In theφ（ethanol）80% extracting solution,a slow but full protein denaturation takes place,which causes the unfolding of protein and the dissociation of drugs.Then K2HPO4was added into the extracting solution to form aqueous two-phase system,and meanwhile the drug residues were extracted into upper phase with high extraction efficiencies.After filtration,the upper phase was ready for analysis of drug residues by HPLC system.The detection limits were in the range of 18.8～38.4ng·mL^-1,and the spiked recovery was 94.2%～98.7%for determination of antipsychotic drugs in human serum.The method is efficient,solvent-saving,environment-friendly,and accurate.