Analytica Chimica Acta 522 (2004) 89–97 Surfactant–dye binding degree method for the determination of amphiphilic drugs Ana Pedraza, Mar´ ıa Dolores Sicilia, Soledad Rubio, Dolores P´ erez-Bendito ∗ Department of Analytical Chemistry, Faculty of Sciences, University of C´ ordoba, Edificio Anexo Marie Curie, Campus de Rabanales, C ´ ordoba 14071, Spain Received 4 June 2004; received in revised form 26 July 2004; accepted 26 July 2004 Abstract The surfactant–dye binding degree (SDBD) method was extended to the determination of amphiphilic drugs. This new methodology was based on the effect of amphiphilic compounds on the degree of binding of a surfactant to dye molecules. The dye induces the formation of surfactant aggregates and allows this process to be monitored from changes in their spectral features. The interaction between the anionic dye Coomassie Brilliant Blue G (CBBG) and the cationic surfactant didodecyldimethylammonium bromide (DDABr) was used for the sensitive determination of phenamic acids (meclophenamic, mephenamic, fluphenamic and niflumic acid), non-steroidal anti-inflammatory drugs. The addition of phenamic acid to the dye–surfactant mixture resulted in the formation of drug–DDABr aggregates with well-defined stoichiometries (between 1:1 and 1:3) and, hence, in decreased interactions between the dye and the cationic surfactant. Mixtures of drug–surfactant were demonstrated to behave as those made up of pure surfactant, and, therefore, the expression previously derived for determining surfactants could be used to quantify amphiphilic drugs. The proposed method permitted the determination of phenamic acids at the mg l -1 level with the precision required for quality control (the relative standard deviation for 7 mg l -1 of meclophenamic acid was 1.1%). Pharmaceutical preparations were analysed directly after dissolution of the samples in ethanol. © 2004 Elsevier B.V. All rights reserved. Keywords: Surfactant–dye binding degree method; Dye-induced surfactant aggregates; Phenamic acids; Pharmaceuticals 1. Introduction Amphiphiles play an essential role in the existence of life and living processes and are widely used in the industry, agri- culture, medicine, pharmacology, etc. [1,2]. All supramolec- ular assemblies produced by spontaneous association of am- phiphiles in aqueous media are characterised by parameters such as the critical aggregation concentration (cmc for mi- celles, cvc for vesicles, etc.), the aggregation number, shape, etc., and therefore these parameters can provide the basis for the development of analytical methodologies of general use in amphiphile determinations, independently on the structure and physical properties of these molecules. ∗ Corresponding author. Tel.: +34 957 218644; fax: +34 957 218644. E-mail address: qa1pebem@uco.es (D. P´ erez-Bendito). Several years ago, we proposed the mixed aggregate (MA) method [3], which is based on the measurement of the critical micelle concentration (cmc) of mixed premicellar and micel- lar aggregates, to determine amphiphiles. At this point, the principles that support the MA method have been established and the strategies devised for increasing sensitivity, selectiv- ity and precision have been discussed [4]. The suitability of this method to determine the total amount of non-ionic [3,5], cationic [6–8] or anionic [9] surfactants (parameters of in- terest in environment and consumer products), additives in foodstuffs [10], drugs in pharmaceuticals [11–13], etc., has been proved, and procedures based on cmc measurements have been developed that notably improve the analytical fea- tures of those based on conventional measurements. Recently, we have extended the use of aggregation param- eters of supramolecular assemblies in the determination of amphiphiles with the development of a new approach, based 0003-2670/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2004.07.056