Journal of Pharmaceutical and Biomedical Analysis 44 (2007) 305–308 Short communication Validation of a capillary electrophoresis method for the analysis of ibandronate related impurities J.A. Bertinatto Rodr´ ıguez, M.F. Desimone, S.L. Iglesias, S.A. Giorgieri, L.E. Diaz ∗ C´ atedra de Qu´ ımica Anal´ ıtica Instrumental, Facultad de Farmacia y Bioqu´ ımica, Universidad de Buenos Aires, Jun´ ın 956 Piso 3 ◦ (1113), Buenos Aires, Argentina Received 8 November 2006; received in revised form 13 February 2007; accepted 16 February 2007 Available online 23 February 2007 Abstract A capillary zone electrophoretic (CZE) method has been developed for the determination of impurities (phosphyte and phosphate) in technical- grade ibandronate, which is a potent nitrogen-containing bisphosphonate. Successful separation of the drug from the impurities was achieved using 1 mM tetradecyl-trimethyl-ammonium bromide (TTAB) and 5 mM potassium chromate (pH 10.0) as background electrolyte with an indirect detection at 254nm. The optimised method was validated for specificity, precision, linearity and accuracy. The limit of detection (LOD) was 2 g/mL and the limit of quantification (LOQ) was 7 g/mL for both phosphyte and phosphate. The developed CZE method used to determine phosphyte and phosphate as bisphosphonates impurities can be used to evaluate the quality of regular production samples of ibandronate. © 2007 Elsevier B.V. All rights reserved. Keywords: Capillary zone electrophoresis; Ibandronate; Impurities determination; Validation 1. Introduction The impurities in drugs often possess unwanted pharmaco- logical or toxicological effects. Therefore, it is quite obvious that the products intended for human consumption must be charac- terized as completely as possible. Thus, the analytical activities concerning impurities in drugs are among the most important issues in modern pharmaceutical analysis [1–3]. In this way the use of high performance liquid chromatography has been found to be a very good technique for many years in pharmaceutical industry [4]. The use of capillary electrophoresis (CE) techniques has become increasingly popular in recent years [5]. CE is a power- ful technique used for the separation of both charged and neutral compounds [6–8]. The wide application range, similar to HPLC, includes assay of drugs [9–11], determination of drugs-related impurities [12–14], analysis of vitamins [15–18] proteins [19] and pharmaceutical excipients [20]. Several advantages can be mentioned in the pharmaceutical analysis using CE, including ∗ Corresponding author. Tel.: +54 11 49648254; fax: +54 11 49648254. E-mail address: ldiaz@ffyb.uba.ar (L.E. Diaz). speed and cost of analysis, reduction in solvent consumption and disposal, and the possibility of rapid method development, and throughput. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy in the treatment of metastic bone disease, including hypercalcemia of malignancy and in the manage- ment of postmenopausal osteoporosis [21]. It is chemically designated as 3-(N-methyl-N-pentyl) amino-1-hydroxypropane- 1,1-diphosphonic acid, monosodium salt, monohydrate. Because there is no chromophore for UV or fluorescence detection and no suitable groups for derivatization, few ana- lytical methods had been described for ibandronate. Previously reported methods applying ion-exchange chromatography [22] or ion-pair reverse-phase liquid chromatography [23] require more than 15 min for the analysis. These methods, though able to determine all the impurities, require sample prepara- tion, derivatization, or preconcentration steps for satisfactory results. This work proposed a validated capillary electrophoresis technique with indirect-UV detection, with low migration times and without sample preconcentration requirements, for the analysis of phosphate and phosphyte, impurities related to nitrogen-containing bisphosphonates. 0731-7085/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jpba.2007.02.021