Substandard /counterfeit drugs represent an expanding problem throughout developing countries with considerable consequences for global public health. This work aimed to provide two simple chromatographic methods for separation and simultaneous determination of meclizine HCl in its mixtures with pyridoxine HCl, caffeine or nicotinic acid. RP-HPLC method was developed using Inertsil C8 column at ambient temperature with flow rate of (1 min mL-1) and UV detection at 230 nm, the mobile phase was composed of 0.1M NaH2PO4 (pH 3):acetonitrile:methanol (40:55:5 v/v/v). Cinnarizine was used as an internal standard. TLC method was developed using a mixture of [glacial acetic acid: dichloromethane: methanol (1.5:5:18.5 v/v/v)] as developing system. The spots were scanned at 230, 292, 273, 262 nm for meclizine HCl, pyridoxine HCl, caffeine and nicotinic acid, respectively. The RP-HPLC method was linear over concentration range of (37.5-200.0), (75.0-400.0), (30.0-160.0) and (75.0-400.0 μg mL-1) for meclizine HCl, pyridoxine HCl, caffeine and nicotinic acid, respectively. The TLC method was linear over the range of (1.25-15), (1-20), (0.4-8) and (1-20 μg spot-1) for meclizine HCl, pyridoxine HCl, caffeine and nicotinic acid, respectively. The method provides sufficient selectivity and accuracy to be applied for routine analysis and quality control in laboratories of the cited drugs.