Available online at www.sciencedirect.com Journal of Pharmaceutical and Biomedical Analysis 46 (2008) 670–675 Optimization and validation of a dissolution test for selegilin hydrochloride tablets by a novel rapid HPLC assay using a monolithic stationary phase Paraskevas D. Tzanavaras a,∗ , Demetrius G. Themelis a , Anastasia Zotou a , John Stratis a , Bo Karlberg b a Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Gre b Department of Analytical Chemistry, Stockholm University, SE-10691 Stockholm, Sweden Received 7 September 2007; received in revised form 7 November 2007; accepted 20 November 2007 Available online 4 December 2007 Abstract The present study reports the optimization and validation of a dissolution test for selegiline·HCl tablets using a new high- chromatographic (HPLC) method. Rapid separation of the analyte from sample matrix was achieved in less than 60 s using ® RP-18e monolithic column using UV detection at 220 nm. Thorough validation of the assay based on pre-defined criteria included li accuracy, precision, selectivity and ruggedness. The dissolution test was optimized in terms of dissolution medium, basket II) agitation and rotation speed. Its ruggedness was also validated. The presented analytical and dissolution procedures are in the quality and stability control of Cosmopril ® tablets (5 mg/tablet selegiline·HCl, Cosmopharm Ltd., Korinthos, Greece). © 2007 Elsevier B.V. All rights reserved. Keywords: Selegiline hydrochloride; Dissolution; High-performance liquid chromatography; Monolithic column; Pharmaceutical analysis 1. Introduction Selegiline hydrochloride, also commonly referred to in the clinicaland pharmacological literature as l-deprenyl, is an acetylenic derivative of phenethylamine. It acts as an irreversible inhibitor of monoamine oxidase (MAO), an intracellular enzyme associated with the outer membrane of mitochondria. This is considered to be of primary importance in the treatment of Parkinson’s disease, although the mechanisms accounting for selegiline’s beneficial adjunctive action are not fully understood [1].Studies have shown that selegiline can also slow the pro- gression of Alzheimer’s disease [2] and that it might be a useful solution to smoking addiction, since itreduces the intensity of nicotine cravings [3]. Since selegiline was the first MAO inhibitor to be approved for the treatment of Parkinson’s disease, concerns were raised about the safety of the drug. These concerns were especially based on previously reported side-effects of non- selective MAO inhibitors. The contacted studies proved that ∗ Corresponding author. Fax: +30 2310 997719. E-mail address: ptzanava@chem.auth.gr (P.D. Tzanavaras). selegiline is well-tolerated when given alone, although minor symptoms such as nausea, headaches and dizziness have b reported during monotherapy. More severe effects – includ mortality – have been reported when selegiline and levodo or pethidine were administered together. Thus, the concom use of these drugs is not recommended [4]. Drug absorption after oral administration of a solid dosa form depends on the release of the active ingredient from formulation, its dissolution under physiological conditions, the permeability across the gastrointestinal tract. Because critical nature of the first two of these steps, in vitro dissol may be relevant to the prediction of in vivo performance [5 It is therefore widely accepted that dissolution testing is a important tool in the pharmaceutical industry for providing able information to both formulation teams that design new ucts and quality control scientists for ensuring lot-to-lot qu and consistency within pre-defined specification criteria [8 A key determinant of the reliability of results of dissolut tests is the validity of the analytical assay used to determine the active pharmaceutical ingredient in test samples. The i method intended for this purpose should be adequately sen sitive,selective against pharmaceutical excipients, robust and 0731-7085/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jpba.2007.11.039