Determination of benzalkonium chloride preservative in pharmaceutical formulation of eye and ear drops using new potentiometric sensors M. Gaber a , Hazem M. Abu Shawish b, ⁎, Abdalla M. Khedr a, ⁎, Khalid I. Abed-Almonem a a Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt b Chemistry Department, College of Sciences, Al-Aqsa University, Gaza, Palestine abstract article info Article history: Received 11 April 2012 Received in revised form 14 June 2012 Accepted 19 June 2012 Available online 26 June 2012 Keywords: Benzalkonium chloride Ion-selective electrode Potentiometry Carbon paste electrodes Pharmaceutical formulation A novel approach for determination of low concentrations of the preservative, benzalkonium chloride (BCCl), in pharmaceutical formulation constitutes is presented. New chemically modified carbon paste electrodes (CMCPEs) are developed. The first is based on an ion-association of BCCl with phosphomolybdic acid (PMA) as the ion-exchanger (BC–PM) dissolved in the mixed plasticizers dibutyl phthalate (DBP) and dioctyl sebacate (DOS) encoded sensor A. In the other electrode, encoded sensor B, the plasticizers DBP and dioctyl phthalate (DOP) are more suitable solvent mediators for the paste. These electrodes exhibit a Nernstian slope of 58.2± 0.6 and 62.3±0.7 mV/decade in concentration range 1.3×10 -7 –1.7×10 -4 M and 2.5×10 -7 –1.7×10 -4 M with the limit of detection of 1.0×10 -7 M and 1.6×10 -7 for sensors A and B, respectively. The sensors have short and stable response time 5–8 s, good reproducibility and can be used in pH range of 5.7–8.6. The present electrodes show good discrimination of BCCl from several inorganic, organic ions and some common drug excip- ients. These characteristics of the electrodes make them useful in successful determination of BCCl in its pharma- ceutical preparations (eye and ear drops) and aqueous solutions. The results obtained were satisfactory with excellent percentage recovery comparable and sometimes better than those obtained by other routine methods for the assay. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Benzalkonium chloride (BCCl), a bactericidal antimicrobial agent, is used as a preservative or disinfectant in over 65% of the ophthal- mic products currently available in the market [1,2]. Its general for- mula is [C 6 H 5 CH 2 N(CH 3 ) 2 C 14 H 29 ]Cl, (Fig. 1). Benzalkonium chloride, also known as alkyl dimethyl benzyl ammonium chloride, is a mix- ture of alkylbenzyldimethylammonium chlorides of various even numbered alkyl chain lengths. This product is a nitrogenous cationic surface-acting agent belonging to the quaternary ammonium group. It has three main categories of use: as a biocide, a cationic surfactant and phase transfer agent in the chemical industry. Its applications are extremely wide ranging, from disinfectant formulations to microbial corrosion inhibition in the oilfield sector. It has been considered as one of the safest synthetic biocides known and has a long history of ef- ficacious use. Its use as a preservative in cosmetics such as eye, ear and nasal drops attests to its general safety [3]. These disinfectants are wide- ly utilized in hospitals and other places, and are often seen around the sinks. Their acute toxicity to fish is 2.0 to 3.5 mg/L (LC 50 ), and toxicity to invertebrates varies from 1.0 to 50 mg/L [4]. Due to ease of its acces- sibility and high risk danger, toxic or fatal cases of accidental ingestion have occurred [5,6]. Therefore, determination of benzalkonium chloride has important practical meanings. Several analytical techniques have been used to evaluate benzal- konium chloride in pharmaceutical products including capillary elec- trophoresis, [4,7] voltammetry, [8] gas chromatography with flame ionization detection [9] and high performance liquid chromatography with UV detection (HPLC-UV) [2,3,10–12]. However, these methods comprise sample manipulations, extraction steps, derivatization reac- tions that are liable to various interferences as well as being not appli- cable to colored and turbid solutions. These methods are expensive for they require large infrastructure backup and qualified personnel. Thus, there is critical need for the development of selective, inexpen- sive diagnostic tool for the determination of this analyte. Analytical methods based on potentiometric detection with ion-selective elec- trodes (ISEs) can be considered good alternatives for their attractable characteristics mentioned above. Chemically modified carbon paste electrodes (CMCPEs) have been successfully applied as potentiometric sensors for determination of various species [13–15]. No potentiometric carbon paste electrode is found for the determi- nation of benzalkonium chloride on careful review of literature. The present work describes construction, potentiometric characterization, and analytical application of two modified carbon paste electrodes se- lective for benzalkonium chloride based on the ion-exchanger, name- ly, benzalkonium phosphomolybdate dissolved in plasticizers dibutyl phthalate (DBP) and dioctyl sebacate (DOS) (sensor A) and another Materials Science and Engineering C 32 (2012) 2299–2305 ⁎ Corresponding authors. E-mail addresses: hazemona1@yahoo.co.uk (H.M. Abu Shawish), abkhedr2001@yahoo.com (A.M. Khedr). 0928-4931/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.msec.2012.06.018 Contents lists available at SciVerse ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec