Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

Abstract

BackgroundAlendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents.ResultsThree simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated.ConclusionThe proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients.Graphical abstract

Osteotropic Therapy via Targeted Layer‐by‐Layer Nanoparticles

“…1H NMR (in D2O): 1.33 – 1.9 ppm [broad signal, poly(acrylic acid)], 2.10–2.40 ppm [broad signal, poly(acrylic acid)], 2.88 ppm (2H, alendronate). The degree of conjugation was estimated according to the assay protocol reported previously after the hydrolysis of the conjugate at pH 10 with 0.1M NaOH [13] . The estimated degree of functionalization was found to be 43.2%.…”

PLGA-linked alendronate enhances bone repair in diaphysis defect model

“…At designated time‐intervals, 500 μl of release solution was obtained from the mixture and replaced with an equal amount of fresh PBS. The concentration of ALN in the released solution was measured using a reported spectrophotometric method (Walash et al ., ).…”

Development and validation of a novel sensitive UV‐direct capillary electrophoresis method for quantification of alendronate in release studies from biomaterials

“…Bisphosphonates (BP) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis, bone resorption‐related diseases such as cancer, and promote fracture repair . However, BP are poorly absorbed in the intestines when administered orally and therefore, high doses are needed to be used, leading to gastrointestinal disorders, chronic renal failure, or osteonecrosis of the jaws .…”

“…), is a difficult task since these compounds lack chromophore groups in their chemical structure. In this context, numerous HPLC‐based methods have been reported for ALN quantitation, where most of them used ALN derivatization in a precolumn or postcolumn system , ion chromatography , inductively coupled plasma , HPLC‐mass spectrometry methods and ultraviolet(UV)‐spectrophotometric methods . Although most of methods previously mentioned reached limits of quantitation (LOQ) in the order of ppb, there are drawbacks associated with the operation costs, high consumption of organic solvents and its consequently cost of discarding, high consumption of sample and reagents, and long analysis time, especially for HPLC methods.…”