邻苯二甲酸二(2-丙基庚)酯分子印迹固相萃取剂的制备及其应用

以邻苯二甲酸二辛酯(DOP)为虚拟模板分子,α-甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EDMA)为交联剂,采用沉淀聚合法制备了对邻苯二甲酸二(2-丙基庚)酯(DPHP)具有高选择性的分子印迹聚合物(MIP)。用紫外分光光度法探索了不同功能单体与模板分子的结合能力,与功能单体丙烯酸(AA)相比,MAA与DOP的结合能力更强,其最佳结合的物质的量比为6∶1。考察MIP对DOP、DPHP、邻苯二甲酸二甲酯(DMP)、邻苯二甲酸二丁酯(DBP)的选择吸附性能,发现该聚合物对DPHP具有更高的选择吸附性。以制备的聚合物为固相萃取填料,结合HPLC分析,考察了淋洗剂与洗脱剂的种类和用量对DPHP回收率的影响。将DPHP甲醇溶液加载至萃取柱后用1 mL甲醇-水(1∶9,v/v)淋洗,5 mL甲醇-乙酸(9∶1,v/v)洗脱,DPHP在分子印迹固相萃取(MISPE)柱上的回收率达到96.8%,而在非印迹固相萃取(NISPE)柱上的回收率仅为52.9%。将建立的MISPEHPLC方法应用于测定兔口服DPHP后不同时间点兔血清中DPHP的浓度,发现其血药浓度的最大值为5.88μg/mL,达峰值时间为4 h,DPHP加标回收率为90.0%~92.0%,相对标准偏差小于5%。

Preparation and application of di(2-propylheptyl) phthalate molecularly imprinted solid-phase extraction sorbent

The molecular imprinted polymer (MIP) with high selectivity to di(2-propylheptyl) phthalate (DPHP) was synthesized by precipitation polymerization with dioctyl phthalate (DOP) as dummy template, methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EDMA) as cross-linker. The binding ability of the template and functional monomer was investigated by UV spectrometry. Compared with the functional monomer acrylic acid (AA), MAA showed stronger binding capacity to DOP and the best combination mole ratio of 6:1. The selective adsorption performance of MIP for DOP, DPHP, dimethyl phthalate (DMP) and dibutyl phthalate (DBP) was investigated using the prepared MIP as high performance liquid chromatographic column packing. It was found that the prepared MIP showed higher retention ability and selectivity for DPHP. Using the prepared MIP as a solid-phase extraction (SPE) sorbent (MISPE), the effects of the type and amount of washing solvent and elution solvents on the recovery of DPHP were investigated. After optimization of MISPE profile, the DPHP extraction recovery of 96.8% was obtained when the following procedures were applied to MISPE cartridge: conditioning with 2 mL methanol, loading with 1 mL methanol, washing with 1 mL methanol-water (1:9, v/v), eluting with 5 mL methanol-acetic acid (9:1, v/v). The recovery of DPHP on non-imprinted polymer (NIP) cartridge was only 52.9%. The developed MISPE-HPLC method was applied to determine the concentrations of DPHP in rabbit serum at different time points after oral administration. It was found that the maximal concentration (c_max) and time (t_max) were 5.88 μg/mL and 4 h, respectively. The recoveries of spiked DPHP in rabbit serum ranged from 90.0% to 92.0% with the relative standard deviations less than 5%。