Walash M I, El-Brashy A, El-Enany N, Wahba M E K
Department of Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Int J Biomed Sci. 2009 Jun;5(2):158-68.
A simple, sensitive and specific method was developed for the determination of famotidine (FMT) in pharmaceutical preparations and biological fluids. The proposed method is based on ternary complex formation of famotidine (FMT) with EDTA and terbium chloride TbCl3 in acetate buffer of pH 4. Alternatively, the complex is formed via the reaction with hexamine and either lanthanum chloride LaCl3, or cerous chloride CeCl3 in borate buffer of pH6.2 and 7.2 respectively. In all cases, the relative fluorescence intensity of the formed complexes was measured at 580 nm after excitation at 290 nm. The fluorescence intensity - concentration plots were rectilinear over the concentration range of 10-100, 5-70, and 5-60 ng/ml, with minimum quantification limits (LOQ) of 2.4, 2.2, and 5.2 ng/ml, and minimum limits of detection (LOD) of 0.79, 0.74, and 1.7 ng/ml upon using TbCl3, LaCl3, and CeCl3 respectively. The proposed method was applied successfully for the analysis of famotidine in dosage forms and in human plasma. The kinetics of both alkaline and oxidative induced degradation of the drug was studied using the proposed method. The apparent first order rate constant and half life time were calculated. A proposal of the reaction pathways is presented.
开发了一种简单、灵敏且特异的方法，用于测定药物制剂和生物流体中的法莫替丁（FMT）。所提出的方法基于法莫替丁（FMT）与乙二胺四乙酸（EDTA）和氯化铽（TbCl3）在pH 4的醋酸盐缓冲液中形成三元络合物。或者，该络合物分别通过与六次甲基四胺以及氯化镧（LaCl3）或氯化铈（CeCl3）在pH 6.2和7.2的硼酸盐缓冲液中反应形成。在所有情况下，在290 nm激发后，于580 nm处测量形成的络合物的相对荧光强度。荧光强度-浓度曲线在10 - 100、5 - 70和5 - 60 ng/ml的浓度范围内呈线性，使用TbCl3、LaCl3和CeCl3时的最低定量限（LOQ）分别为2.4、2.2和5.2 ng/ml，最低检测限（LOD）分别为0.79、0.74和1.7 ng/ml。所提出的方法成功应用于剂型和人血浆中法莫替丁的分析。使用该方法研究了药物碱性和氧化诱导降解的动力学。计算了表观一级速率常数和半衰期。提出了反应途径。
