Pharmaceutical Chemistry Department, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
J Chromatogr A. 2012 Dec 28;1270:9-19. doi: 10.1016/j.chroma.2012.10.038. Epub 2012 Oct 23.
The main objective of this research was computational designing of an imprinted polymer for selective solid phase extraction (SPE) of methadone from plasma and saliva samples analyzed by gas chromatography-flam ionization detector (GC-FID). The density functional theory (DFT) at B3LYP/6-31G+ (d, p) level and Gaussian 2003 package was used to calculate the interaction energy of template-monomers (ΔE). The effect of polymerization solvent was also studied using polarizable continuum model (PCM). It was shown that, methacrylic acid (MAA) gave the largest ΔE in acetonitrile as a polymerization solvent. To examine the validity of this approach, two MIP were synthesized for methadone as template molecule and methacrylic acid as functional monomer in acetonitrile (AN) and methanol (MeOH), respectively. The performance of each polymer was evaluated by using imprinting effect. As it is expected, the best results were obtained for the molecularly imprinted polymer (MIP) which was prepared in AN. For the optimized method, the linearity between responses (peak areas) and concentration of methadone in plasma and saliva samples were found over the range of 3.6-40,000 ng mL(-1) (R(2)=0.997) and 3.0-40,000 ng mL(-1) (R(2)=0.998), respectively. The limit of detection (LOD) and limit of quantification (LOQ) for methadone in plasma were calculated to be 2.45 and 3.6 ng mL(-1), respectively. The LOD and LOQ for methadone in saliva were 2.14 and 3.0 ng mL(-1), respectively. The relative standard deviation (RSD; n=4) for plasma samples containing 10, 100, 500, 1000 ng mL(-1)of methadone were 5.98, 5.78, 5.52, 4.78, 4.74, and the RSD (n=4) for saliva sample containing 5, 20, 100, 1000 ng mL(-1) of methadone were 4.74, 5.1, 5.9, 5.6, respectively.
本研究的主要目的是通过气相色谱-火焰电离检测（GC-FID）对血浆和唾液样本进行分析，计算出用于选择性固相萃取（SPE）的印迹聚合物。在 B3LYP/6-31G+（d，p）水平和 Gaussian 2003 包中使用密度泛函理论（DFT）来计算模板-单体的相互作用能（ΔE）。还使用极化连续模型（PCM）研究了聚合溶剂的影响。结果表明，在作为聚合溶剂的乙腈中，甲基丙烯酸（MAA）给出了最大的ΔE。为了检验这种方法的有效性，分别以甲基丙烯酸为功能单体，在乙腈（AN）和甲醇（MeOH）中合成了两种印迹聚合物（MIP）作为模板分子。通过印迹效应评估每种聚合物的性能。正如预期的那样，在 AN 中制备的分子印迹聚合物（MIP）获得了最佳结果。对于优化后的方法，在血浆和唾液样本中，药物浓度在 3.6-40000ng mL(-1)（R(2)=0.997）和 3.0-40000ng mL(-1)（R(2)=0.998）范围内，药物的响应（峰面积）与浓度之间呈现线性关系。计算出药物在血浆中的检测限（LOD）和定量限（LOQ）分别为 2.45 和 3.6ng mL(-1)。药物在唾液中的 LOD 和 LOQ 分别为 2.14 和 3.0ng mL(-1)。含有 10、100、500、1000ng mL(-1)药物的血浆样品的相对标准偏差（RSD；n=4）分别为 5.98、5.78、5.52、4.78、4.74，含有 5、20、100、1000ng mL(-1)药物的唾液样品的 RSD（n=4）分别为 4.74、5.1、5.9、5.6。
