Stability-Indicating LC Method for the Determination of Lacidipine in Tablets. Application to Degradation Kinetics and Content Uniformity Testing Fathalla Belal, Amina Elbrashy, Manal Eid & , Jenny Jeehan Nasr Department of Analytical Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt; E-Mail: manal_eid@yahoo.com; nasrjj@yahoo.com Received: 12 July 2008 / Revised: 31 December 2008 / Accepted: 17 February 2009 Abstract A simple, stability-indicating, reversed-phase liquid chromatographic method was developed for the determination of lacidipine in the presence of its degradation products. The analysis was carried out using a 150 mm 9 4.6 mm i.d., 5 lm particle size Nucleodur MN-C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer (70:30) at pH = 5.0 was pumped at a flow rate of 1 mL min -1 with UV-detection at 254 nm. The method showed good linearity in the range of 0.06–15 lg mL -1 with a limit of detection (S/N = 3) of 0.016 lg mL -1 (3.5 9 10 -8 M). The suggested method was successfully applied for the analysis of lacidipine in bulk and in commercial tablets with average recoveries of 100.19 ± 0.81% and 100.05 ± 0.69%, respectively. The results were favor- ably compared to those obtained by a reference method. The suggested method was utilized to investigate the kinetics of alkaline, acidic, peroxide and photo-induced degradation of the drug. The apparent first-order rate constant, half-life times and activation energies of the degradation process were calculated. The pH profile curve was derived. The proposed method was successfully applied to the content uniformity testing of tablets. Keywords Column liquid chromatographic Content uniformity testing Stability-indicating and degradation-kinetics Lacidipine Introduction Lacidipine, chemically designated as (E4-{2-[3-(1,1-dimethylethyloxy)-3-oxo- 1-propenyl]phenyl}-1,4-dihydro-2,6-di- methyl-3,5-pyridine-dicarboxylic acid diethyl ester) (Fig. 1) is a calcium chan- nel blocker developed for oral adminis- tration for use in mild to moderate hypertension, and is widely used in therapy since the early 1990s. Lacidipine has also shown anti-atherosclerotic and antioxidant effects. It is one of the most vascular selective of the dihydropyri- dines. It has a long duration of action because of its high degree of lipophilic- ity. The active trans form is used in therapy [1–3]. Several methods have been reported for the quantitative determination of lacidipine in tablets including spectrophotometry [4–7], oxi- dimetry [8], TLC [9], electrochemistry [10, 11], LC [12, 13]. Only few methods have been re- ported for the stability study of lacidi- pine, these included fractional wavelet analysis [14], derivative spectrophotom- etry [15] and normal phase LC [16] for the photodegradation of lacidipine whereas reversed phase LC [13] was used for the stability study of lacidipine to- wards light, temperature and humidity. Several other methods have been re- ported for the determination of lacidi- pine among other dihydropyridines, these include micellar electrokinetic chromatography [17], LC with ampero- metric detection [18, 19], LC-mass spec- trometry [20, 21] and LC with diode array detector using experimental design [22–24]. The aim of the present work was to develop a validated stability-indicating method for the determination of lacidi- pine in the presence of its alkaline, acidic DOI: 10.1365/s10337-009-1067-2 Ó 2009 Vieweg+Teubner | GWV Fachverlage GmbH Original