DRUGS, COSMETICS, FORENSIC SCIENCES Spectrophotometric Analysis of Selective Serotonin Reuptake Inhibitors Based on Formation of Charge-Transfer Complexes with Tetracyanoquinodimethane and Chloranilic Acid IBRAHIM A. DARWISH and IBRAHIM H. REFAAT Assiut University, Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, Assiut 71526, Egypt A simple, accurate, and sensitive spectrophotometric method for analysis of selective serotonin reuptake inhibitors (SSRIs) has been developed and validated. The analysis was based on the formation of colored charge-transfer complexes between the intact molecule of SSRI drug as an n-electron donor and each of tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (pCA) as electron acceptors. The formed complexes were measured spectrophotometrically at 842 and 520 nm for TCNQ and pCA, respectively. Different variables and parameters affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9975–0.9996) were found between the absorbances and the concentrations of the investigated drugs in the concentration ranges of 4–50 and 20–400 mg/mL with TCNQ and pCA, respectively. With all the investigated drugs, TCNQ gave more sensitive assays than pCA; the limits of assay detection were 2.5–4.8 and 20–40 mg/mL with TCNQ and pCA, respectively. The intra- and interassay precisions were satisfactory; the relative standard deviations did not exceed 2%. The proposed procedures were successfully applied to the analysis of the studied drugs in pure form and pharmaceutical formulations with good accuracy; the recovery values were 98.4–102.8 ± 1.24–1.81%. The results obtained from the proposed method were statistically comparable with those obtained from the previously reported methods. S elective serotonin reuptake inhibitors (SSRIs) have been recently introduced for treatment of depression. The SSRIs are comparable to the tricyclic antidepressants in their clinical efficacy, however, they are more safe and have greater acceptance by the patients. Therefore, SSRIs have become the most widely prescribed antidepressants (1, 2). Five SSRIs are presently available: citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; their chemical structures are given in Figure 1. Some SSRIs have also been introduced for other indications, such as obsessive compulsive disorders (3), panic attacks (4), and social phobia (5). The therapeutic importance of SSRIs was behind the development of numerous methods for their quantitative determination. The methods adapted to the analysis of SSRIs in biological fluids have been reviewed (6). The sophisticated instrumentation of these methods limited their use in quality control laboratories for analysis of these drugs in their pharmaceutical formulations. The methods reported for analysis of 1 or more of the SSRIs in pharmaceutical formulations include titrimetry (7, 8), voltammetry (9–11), polarography (12, 13), capillary electrophoresis (14), and liquid chromatography (LC; 15–20). These methods were associated with some drawbacks, such as being time consuming and/or requiring too expensive instruments that are not available in most quality control laboratories. In spite of the inherent simplicity of spectrophotometry and its availability in almost all the quality control laboratories, the spectrophotometric methods reported for analysis of SSRIs in their pharmaceutical formulations (20–29) suffered from the disadvantages of decreased specificity (20, 21), multiple laborious steps (22–25), and/or long analysis time (26, 27). Moreover, these methods have been developed individually because of the wide differences in the chemical structures of SSRIs. Considering these drawbacks, there was a growing interest in the development of more advantageous spectrophotometric method for determination of SSRIs in their pharmaceutical formulations. In a previous study (30), a simple and sensitive spectrophotometric method was developed for determination of SSRIs that possess a secondary amine moiety in their structures (fluoxetine, paroxetine, and sertraline). However, the availability of a spectrophotometric method that allows the analysis of all SSRIs drugs would be useful for economic and convenience reasons. Therefore, the aim of the present study was directed to the development of new spectrophotometric procedures that could be applied for analysis of all members of the SSRI group, irrespective of the diversity in their chemical structure. The analytical procedures described herein were based on the formation of colored charge-transfer complexes between the intact molecules of 326 DARWISH &REFAAT:JOURNAL OF AOAC INTERNATIONAL VOL. 89, NO. 2, 2006 Received May 22, 2005. Accepted by JM July 4, 2005. Corresponding author's e-mail: iadarwish@yahoo.com Downloaded from https://academic.oup.com/jaoac/article/89/2/326/5657598 by guest on 10 November 2022