Chlorproamide (CLP) is a sulphonyl-urea derivative used in the treatment of type 2 diabetes mellitus. A rapid, sensitive and specific HPLC method with uv detection is described for the determination of CLP in bulk and tablet forms. The assay was performed on an Inertsil ODS 3V (150mm × 4.6mm; 5µm particle size) column using a mixture of phosphate buffer (pH 4.5), methanol and acetonitrile (30:63:7v/v/v) as mobile phase at a flow rate of 1mLmin -1 and with uv detection at 254nm. The column temperature was 30ᴼC and injection volume was 20µL. The retention behaviour of CLP as a function of mobile phase pH, composition and flow rate was carefully studied, and chromatographic conditions, yielding a symmetric peak with highest number of theoretical plates, were optimized. The calibration curve was linear (r = 0.9999) over the concentration range 0.5 -300 µgmL -1 . The limits of detection (LOD) and quantification (LOQ) were found to be 0.1 and 0.3 µgmL -1 , respectively. Both intra-day and inter-day precisions determined at three concentration levels were below 1.0% and the respective accuracies expressed as %RE were ≤1.10%. Assays were performed under slightly altered chromatographic conditions, and the results were not significantly different from those obtained under optimum conditions, reflecting the robustness of the method. Inter-equipment and interanalysts deviations were insignificant testifying the ruggedness of the method. The method was validated for selectivity via placebo blank and synthetic mixture analyses. The method was applied to determine CLP in tablets and the results were comparable with those obtained by a reference method with respect to accuracy and precision. As part of stress testing, CLP was subjected to forced degradation under acid and base-induced hydrolysis, oxidation, heat and light, followed by assay using the developed method, and the results indicated that the drug was prone to oxidative degradation, but inert to other stress-conditions. The method was sensitive and selective enough to determine the drug content in spiked urine, and the results were satisfactory.Keywords: Chlorpropamide; Assay; HPLC; Pharmaceuticals; Stabilityindicating Pharmacopeia [16] which has adopted an HPLC-uv detection method for the assay of CLP. British Pharmacopeia [17] describes a spectrophotometric method whereas European Pharmacopeia [18] offers a titrimetric method for the assay in tablets and bulk drug, respectively. In addition to the above, CLP in pharmaceuticals has been assayed by several other techniques such as titrimetry [19], spectrophotometry [20][21][22][23], electrophoresis [24], thinlayerchromatoghraphy [25,26] and coulometry [27].HPLC, which finds immense applications in the analysis of body fluids for CLP [2][3][4][5][6][7], has also been applied to the determination of drug in pharmaceuticals, chiefly due to its sensitivity, selectivity, speed and wide applicability. El-Gizawy [28] has reported an HPLC method for the determination of CLP in tablets. The author used a Zorbax SAX ...