Sildenafil citrate is a potent and selective inhibitor of cGMP (type V)-specific phosphodiesterase capable of enhancing relaxation of the penile corpus cavernosum, and therefore having the potential to improve penile erectile function. 1 The activity of Sild is as an efficacious, orally active agent for the treatment of male erectile dysfunction, and is thus so currently being applied widely to clinical treatments. 2, 3 At present, most of the methods for the determination of Sild are based on

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... PLC, 4-9 and electrochemistry. 10,11 However, the procedures for many methods are not simple due to a preseparation required frequently before determining Sild; also, the sensitivity of some methods is not high enough. Dinesh et al. 12 reported an extractive spectrophotometric method for the determination of Sild with acid triphenylmethane dyes. The sensitivity of this method was insufficient and double extraction was required. Thus, further developing a highly sensitive, simple and rapid method for the determination of Sild is important. In recent years, resonance Rayleigh scattering (RRS) as a new analytical technique has been applied to investigate and determine some inorganic ions 13-15 and biological macromolecules, such as nucleic acid, 16-18 protein, 19-21 heparin 22,23 and medicines. [24] [25] [26] [27] [28] In this work, we found that in a weak acid aqueous solution, the RRS for Sild alone as an organic cation or Evans Blue (EB), itself, as an organic anion was weak. However, when two agents reacted with each other to form ion-association complexes by virtue of electrostatic and hydrophobic interaction forces, the RRS intensity could be greatly enhanced and a new RRS spectrum was observed. The intensity of RRS was directly proportional to the concentration of Sild in the range 0 -11.5 μg ml -1 . The method had high sensitivity and the detection limit for the sild was 30.3 ng ml -1 . In the present work, the spectral characteristics of RRS, the influence of various factors, optimum conditions of interaction, and the properties of analytical chemistry were investigated. A new method for the determination of Sild in a pharmaceutical formulation based on the RRS of the ion-association complex has been developed. Furthermore, the interaction mechanism was considered. Experimental Apparatus and reagents A Shimadzu RF-540 Fluorospectrophotometer (Kyoto, Japan) was used for recording the RRS spectrum. A UV-VIS 8500 spectrophotometer (Tianmei Co., Shanghai, China) was used for recording the absorption spectrum. A pHs-3C acidimeter (Shanghai Dazhong Analytical Instrumental Plant, China) was used for adjusting of the pH value. A 1.0 × 10 -3 mol l -1 stock solution of Sild (offered by West China College of Medicine, Sichuan University, purity 99.9%) was prepared using water and the dilution was made to the 66.6 μg ml -1 working solution. EB (Fluka Co., Switzerland) aqueous 819 ANALYTICAL SCIENCES JUNE A highly sensitive resonance Rayleigh-scattering (RRS) method for the determination of sildenafil citrate has been developed, based on the fact that sildenafil (Sild) reacted with Evans Blue (EB) to form an ion-association complex in pH 1.1 -4.6 aqueous solution. This resulted in a significant enhancement of the RRS intensity, and a new spectrum appeared. The wavelength of the maximum RRS was at 365 nm, and other scattering peaks were at 400, 442, 470 and 534 nm, respectively. The intensity of RRS was directly proportional to the concentration of Sild in the range 0 -11.5 μg ml -1 , and the detection limit for Sild (3σ) was 30.3 ng ml -1 . The composition of the ion-association complex was Sild:EB = 1:1, as established by Job's method. The method had good selectivity and could be applied to the determination of Sild in the aqueous phase without using organic solvent extraction. The method was simple and rapid. In addition, the reaction mechanism and the reason for RRS enhancement were considered.