High-throughput method for the analysis of venlafaxine in pharmaceutical formulations and biological fluids, using a tris(2,2′ -bipyridyl) ruthenium(II)–peroxydisulphate chemiluminescence system in a two-chip device Haider A. J. Al Lawati,* Gouri B. Varma and Fakhr Eldin O. Suliman ABSTRACT: A simple, rapid and sensitive chemiluminescent (CL) method for the assay of venlafaxine (VEN) in pharmaceutical formulations and serum samples by a two-chip device is proposed. The method is based on the reaction of this drug with a tris(2,2′-bipyridyl) ruthenium(II)–peroxydisulphate CL system. The optimum chemical conditions for CL emission were inves- tigated. The calibration graph was linear for the concentration range 0.02–8.0 mg/mL. The detection and quantification limits were found to be 0.006 and 0.018 mg/mL, respectively, while the relative standard deviation (RSD) was <2.0%. The present CL procedure was applied to the determination of VEN in pharmaceutical formulations and serum samples; the recovery levels were in the range 96.5–101.2%. The results suggest that the method is unaffected by the presence of common formulation excipients found in these samples. Copyright © 2012 John Wiley & Sons, Ltd. Keywords: microfluidics; venlafaxine; chemiluminescence; two-chip device; Tris(2,2′-bipyridyl) ruthenium(II) Introduction Venlafaxine (VEN) {1-[2-(dimethylamino)-1-(4-methoxy-phenyl) ethyl] cyclohexanol hydrochloride} belongs to the pharmaco- dynamic class of dual serotonin and noradrenaline reuptake inhibitors (SNRIs), and is used in the treatment of psychiatric disorders (1,2). A number of methods have been developed for the determina- tion of VEN in pharmaceutical samples and biological fluids (1–16). Most of these methods are based on liquid chromatography–mass spectrometric (LC–MS) techniques or tandem MS (1–8). Some of these methods are for the stereoselective determination of VEN (1,2). However, such methods are less important for quality control laboratories, as the drug is administered as a racemate and both enantiomers exhibit pharmacological activity (1). Addi- tionally, these methods rely on expensive instrumentation and require skillful labour; moreover, most of the LC–MS methods developed require sample pretreatment for the analysis of bio- logical fluids (1–8). Several methods have been developed using high-performance liquid chromatography (HPLC) coupled to a UV detection system (9–11). The total run time is usually long and these UV detection- based methods are not very sensitive; detection limits as high as 150 ng/mL have been reported (9). Such a high detection limit restricts their use in the determination of VEN in biological fluids. To overcome this problem, an HPLC–fluorescence (FL) detection system has been developed for the analysis of VEN, mainly in biological samples (12–14). The sensitivity is significantly improved and detection limits as low as 0.3 ng/mL have been reported (12). However, despite the use of HPLC as the separation technique, an extraction method is still required prior to the analysis of the biological samples. Additionally, the use of an internal standard calibration method increases the cost of analysis and adds complexity to the method. Therefore, the total run time of these HPLC–FL methods is usually long and hence limits their use in quality control laboratories (12–14). Only one high-throughput method has been developed for the quantitative determination of drugs in pharmaceutical or biological samples using spectrophotometric measurements. However, the detection limit of the method is high (150 ng/mL), while the throughput of 30/h could be improved (15). A static chemiluminescence (CL) method has also been devel- oped and a good detection limit was obtained (3.8 ng/mL). However, static CL is not very attractive, as it suffers from being laborious and has a low-throughput (16). Here we propose a Ru(bipy) 3 2+ peroxydisulphate CL system in a two-chip device. The device has been described in detail elsewhere (17); briefly, it consisted of chip 1, which is used as a microphotochemical reactor. In this chip, Ru(bipy) 3 2+ was mixed with peroxydisulphate to produce Ru(bipy) 3 3+ . The resultant solution was pumped to meet VEN solution in chip 2 (Fig. 1). A strong CL signal was then obtained when VEN reacted with * Correspondence to: H. A. J. Al Lawati, Department of Chemistry, College of Science, Sultan Qaboos University, Box 36, Al-Khod 123, Oman. E-mail: haiderl@squ.edu.om Department of Chemistry, College of Science, Sultan Qaboos University, Al-Khod, Oman Luminescence 2012 Copyright © 2012 John Wiley & Sons, Ltd. Research article Received: 17 July 2011, Revised: 30 September 2011, Accepted: 06 December 2011, Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/bio.2334