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Simple, repaid and accurate zero-, first- and second-order derivative spectrophotometric methods have been developed for determination of chlorthalidone (CLT) in commercially available tablets. Normal spectrophotometric scan (zero order) shows maximum absorbance at 276 nm in methanol solution and a good linearity in the range of 10.0–75.0 μg/mL. Linear relations using first (D1) and second (D2) order derivative methods were obtained at 278 and 288 nm for D1 and 286 and 292 nm for D2.The calibration curves were constructed in the range of 1.0–25.0 μg/mL for D1 (R = 0.998) and D2 (R = 0.999). Different analytical validations were determined (accuracy, precision, specificity, recovery, stability and robustness) to demonstrate its suitability for routine quality control labs. All the developed methods were successfully applied to a tablet formulation and the results were compared statistically with each other and with those obtained by the HPLC reference method

Spectrophotometric determination of chlorthalidone in pharmaceutical formulations using different order derivative methods