Spectrophotometric determination of alendronate in pharmaceutical formulations via complex formation with Fe(III) ions

doi:10.1016/S0731-7085(02)00021-3

Journal of Pharmaceutical and Biomedical Analysis

Volume 28, Issue 6, 15 June 2002, Pages 1215-1220

https://doi.org/10.1016/S0731-7085(02)00021-3 Get rights and content

Abstract

The formation of the complex between alendronate, non-chromophoric bisphosphonate drug important for the treatment of a variety of bone diseases, and iron(III) chloride in perchloric acid solution was studied. The stoichiometric ratio of alendronate to Fe(III) ions in the chromophoric complex was determined to be 1:1. The conditional stability constant was $log K′_{ave} =4.50 (SD =0.15)$ , indicating that the Fe(III)–alendronate complex is a complex of medium stability. The optimum conditions for this reaction were ascertained and a spectrophotometric method was developed for the determination of alendronate in the concentration range 8.1–162.5 μg ml⁻¹, the detection limit being 2 μg ml⁻¹. The method was validated for the direct determination of alendronate in tablet dosage formulations.

Introduction

The bisphosphonates, long-lived synthetic analogs of pyrophosphates, have been investigated over the past two decades for the treatment of various bone diseases and calcium metabolism [1]. The parent compound, etidronate, was first used in multicentered trials for treatment of primary osteoporosis. The recently approved drug alendronate is a more potent agent than etidronate in producing a greater increase in bone density. This agent is currently the bisphosphonate of choice for clinical use in treatment of osteoporosis, Paget's disease, primary hyperparathyroidism, hypercalcemia of malignancy and metastatic bone disease [2], [3], [4].

The trihydrate of alendronate sodium having highly ionic character do not possess an appreciable chromophore, hence the determination by ordinary spectrophotometric method is not possible. Methods for its determination in pharmaceutical formulations are based on liquid chromatography–mass spectrometry [5], ion chromatography with indirect UV detection [6], [7] or conductivity detection [8], capillary electrophoresis [9] and inductively coupled plasma [10]. Quantification of alendronate in biological fluids was performed by HPLC with fluorescence and electrochemical detection [11]. Formation of chromophoric complex between alendronate and copper(II) ions in acidic media was applied to analytical method development [9], [12].

The present paper describes a simple and reproducible assay for the determination of alendronate in dosage forms. The method is based on the formation of a chromophoric complex of the drug with Fe(III) ions. Its advantages over already existing methods are rapidness, simplicity and inexpensiveness.

Section snippets

Instruments

Perkin–Elmer Lambda 5 and 15 UV–Vis spectrophotometer with 10 or 20 mm quartz cells were used for spectrophotometric measurements.

Materials

Working standard alendronate sodium trihydrate (Merck Sharp & Dohme International, USA), Alendronat tablets (Zdravlje, Leskovac) containing 13.6 mg of alendronate sodium trihydrate and lactose, maize starch and magnesium stearate as excipient, ferric chloride hexahydrate (Merck) and perchloric acid (Merck) were used. Water purified by a Millipore Milli-Q system was

Absorption spectra and stoichiometry of the Fe(III)–alendronate complex

The complex formation between Fe(III) ions and alendronate was investigated in the acidity range from 0.05 to 2 M HClO₄. Highly acidic medium was necessary in order to avoid the hydrolysis of Fe(III) ions [15]. The absorption spectra of the Fe(III)–alendronate complex recorded in the wavelength range from 200 to 400 nm are shown in Fig. 1 (curves c–i). For comparison, the absorption spectra of the reacting species (alendronate and Fe(III) ions) are also given in Fig. 1 (curves a and b,

Conclusions

The spectrophotometric method described was found to be simple and sensitive and therefore could be applied for the determination of alendronate in the bulk drug and in Alendronat tablets. The results obtained confirm the suitability of the proposed method for the precise analysis of alendronate. Since this method is rapid, simple and no expensive laboratory technique is needed, it can be used for routine analyses.

However, as a non-separative method its main disadvantage is the inability to

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Citation Excerpt :
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Short communicationSpectrophotometric determination of alendronate in pharmaceutical formulations via complex formation with Fe(III) ions

Abstract

Introduction

Section snippets

Instruments

Materials

Absorption spectra and stoichiometry of the Fe(III)–alendronate complex

Conclusions

Am. J. Med. Sci.

J. Chromatogr. A

J. Pharm. Biomed. Anal.

J. Chromatogr.

J. Chromatogr.

J. Pharm. Biomed. Anal.

J. Chromatogr. Biomed. Appl.

Am. Fam. Physician

Am. J. Manage. Care

Short communication
Spectrophotometric determination of alendronate in pharmaceutical formulations via complex formation with Fe(III) ions