Online Postcolumn Indirect Detection for Determination of Ibandronate in Pharmaceutical Tablets by HPLC/DAD
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Ibandronate sodium monohydrate is a highly polar aliphatic compound that belongs to the bisphosphonate class, a widely used bone resorption inhibitor. The aliphatic nature of ibandronate precludes direct photometric detection and its high polarity urged analysts to use ion-pairing agents in the mobile phase to promote retention in reversed-phase columns. In this work, a reversed-phase method for determination of ibandronate sodium monohydrate in pharmaceutical tablets is introduced by employing an online postcolumn ligand exchange reaction to enable photometric detection. The method offers for the first time the ability to separate the drug from its well-known impurities on conventional reversed-phase columns. The detection reaction depends on the ability of ibandronate and its degradation products to displace salicylate in the iron(III) salicylate complex, forming various colorless iron (III) complexes and showing a negative chromatographic signal for ibandronate and its degradants at λmax = 525 nm. The chromatographic separation was achieved using a Hypersil BDS C8 column (5 µm particle size, 150 mm × 4.6 mm i.d.) and a mobile phase consisting of a mixture of aqueous formate buffer pH 3 (pH 3, 5 mM) and methanol in a ratio of 80:20% (v/v), delivered at a flow rate of 0.8 mL/min. The postcolumn iron(III) salicylate reagent was prepared at 250 µM in aqueous formate buffer, delivered using a syringe pump at a flow rate of 0.5 mL/min. The proposed method was validated as per the guidelines of the International Conference on Harmonization Q2(R1) and was found linear over the range 40–120 µg/mL (r = 0.9995) with a limit of detection of 3.19 µg/mL. Compared to currently reported methods, the proposed method is considerably simpler, faster, cheaper, and adequately sensitive and makes use of the most popular LC detectors.
KeywordsBisphosphonates Non-chromophoric drugs Highly polar compounds High-performance liquid chromatography Reversed phase
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Conflict of interest
The authors declared no conflict of interests.
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All the authors gave their consent for the publication of this article.
The experiments were conducted according to the rules of the Ethical Committee of the Faculty of Pharmacy, Tanta University, Egypt. No studies with human participants or animals were performed by any of the authors in this work.
- 1.Sambrook P, Seeman E, Phillips S, Ebeling P. Preventing osteoporosis: outcomes of the Australian fracture prevention summit. Med J Aust. 2002;176:1–16.Google Scholar
- 4.Hu MY, Zhou XQ, Wang BC. Determination of ibandronate by high performance ion exchange chromatography. Chin J Chromatogr. 2000;18:254–5.Google Scholar
- 9.Narendra Kumar M, Pavan Kumar KSR, Jagadeesh Kumar V, John Prasanna S, Kumar Sharma H, Krishna Reddy V. Stability indicating ion chromatography method for the simultaneous determination of ibandronate sodium drug substance and its impurities. J Pharm Biomed Anal. 2011;54:596–601.CrossRefGoogle Scholar
- 11.Mabrouk M, Hammad SF, Abdelaziz MA, Mansour FR. Indirect spectrophotometric determination of ibandronate in pharmaceutical formulations via ligand exchange. Anal Chem Lett. 2019;8:1–6.Google Scholar
- 15.Mabrouk M, Hammad SF, Abdelaziz MA, Mansour FR. Determination of etidronate in pharmaceutical formulations by RP-HPLC method with indirect UV detection. Arab J Med Sci. 2018;1:1–4.Google Scholar
- 17.ICH. Validation of analytical procedures: text and methodology Q2 (R1). In: International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. 2005. p. 1–13.Google Scholar