212 Summary A simple and sensitive thin-layer chromatographic method has been established for analysis of bupropion hydrochloride in pharmaceu- tical tablets. Chromatography on silica gel 60 F 254 plates with 30:10:1 (v/v) ethanol–chloroform–glacial acetic acid as mobile phase furnished compact spots at R F 0.56 ± 0.01. Densitometric analysis was performed at 254 nm. To show the specificity of the method bupropion hydrochloride was subjected to acid and alkaline hydrol- ysis, oxidation, photodegradation, and dry and wet heat treatment; peaks of degradation products were well resolved from that of the pure drug. Linear regression analysis revealed a good linear rela- tionship between peak area and amount of bupropion hydrochlo- ride in the range 200–1000 ng per band. The limits of detection and quantitation were 11.45 and 34.71 ng per band, respectively. The method was validated, in accordance with ICH guidelines, for preci- sion, accuracy, robustness, and ruggedness. The intra-day and inter- day repeatability of the method, as RSD, was approximately 1-2%, showing method precision was sufficient. Method recovery was between 102.07 and 104.58% and between 97.20 and 102.19% for quality-control standards and for bupropion hydrochloride in a synthetic mixture, respectively. Statistical comparison of results with those obtained from HPLC analysis proved the method is reproducible and enables selective analysis of bupropion hydrochlo- ride in pharmaceuticals. Because the method could effectively sepa- rate the drug from its degradation products, it can be regarded as stability indicating. 1 Introduction Bupropion hydrochloride (BUP), (±)-2-(tert-butylamino)-3’- chloropropiophenone hydrochloride (Figure 1) is an aminoke- tone derivative with a pK a of 7.9 [1]. It is a second-generation antidepressant agent with neurochemical properties different from those of conventional tricyclic antidepressants. It has been reported that BUP is a selective inhibitor of neuronal reuptake of catecholamines (noradrenalin and dopamine) with minimum effect on reuptake of indolamines (serotonin) and no inhibitory effect on monoamine oxidase. BUP in sustained release form is used in smoking cessation as the first licensed non-nicotine pharmacological therapy [2]. Several chromatographic methods have been reported for the analysis of BUP in biological fluids, including high-perfor- mance liquid chromatography (HPLC) [1, 3–6] and liquid chro- matography–tandem mass spectrometry (LC–MS) [7]. Chiral separation of the enantiomers of BUP on an ovomucoid column has also been reported [8]. By use of Cooper’s method, the sta- bility of BUP in human plasma and pharmacokinetic profiles in different animal models have been determined [9, 10]. A few chromatographic methods, including HPLC [11, 12], gas chro- matography [13], and electrokinetic chromatography [14] have been reported for analysis of BUP in pharmaceutical formula- tions. A thin-layer chromatographic (TLC) method, in the BUP monograph in USP XXIX, is available for analysis of its degra- dation product, m-chlorobenzoic acid, and related impurities. In this method, the spots were applied to 0.25-mm layer of high- performance silica gel and chromatographed with the mobile phase toluene–cyclohexane–glacial acetic acid 47:47:6 (v/v) [15]. As we are aware, no TLC method for analysis of BUP in pharmaceutical preparations has been reported in the literature. The objective of this study was to establish, in accordance with ICH guidelines [16], a simple, accurate, specific and repro- ducible TLC method which could be used for analysis of BUP in pharmaceutical preparations, in the presence of its degradation products. D. Yeniceli, D. Dogrukol-Ak, Anadolu University, Faculty of Pharmacy, Depart- ment of Analytical Chemistry 26470 Eskisehir, Turkey. E-mail: dak@anadolu.edu.tr A Validated Thin-Layer Chromatographic Method for Analysis of Bupropion Hydrochloride in a Pharmaceutical Dosage Form Duygu Yeniceli and Dilek Dogrukol-Ak* Key Words Bupropion hydrochloride Thin-layer chromatography (TLC) Method validation Stability Tablet analysis Figure 1 Chemical structure of BUP. Journal of Planar Chromatography 23 (2010) 3, 212–218 DOI: 10.1556/JPC.23.2010.3.9 0933-4173/$ 20.00 © Akadémiai Kiadó, Budapest