Efforts toward the synthesis and process optimization of amtolmetin guacil 1 are described. High-yielding electrophilic substitution followed by Wolf-Kishner reduction are the key features in the novel synthesis of tolmetin 2 which is an advanced intermediate of 1.

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A novel stability indicating isocratic, reversed phase-liquid-chromatographic method has been developed for the simultaneous quantitative determination of Arterolane maleate And Piperaquine phosphate in combined-dosage form. A thermo hypersil BDS C18 (250*4.6*5µ) column with mobile phase containing water pH 2.8 adjusted with ortho phosphoric acid: methanol in the ratio of (60: 40, v/v) was used. The flow rate was 1.0 mL/min, column temperature was 30°C and effluents were monitored at 241 nm. The retention times of Arterolane Maleate and Piperaquine Phosphate were 1.864min and 3.047min, respectively. Correlation co-efficient for Arterolane Maleate and Piperaquine Phosphate was found to be 0.99 and 0.99, respectively. The proposed method was validated with respect to linearity, accuracy, precision, specificity, and robustness. Recovery of Arterolane Maleate and Piperaquine Phosphate in formulations was found to be in the range of 97-103% and 97-103% respectively confirms the non-interferences of the excipients in the formulation. Arterolane Maleate and Piperaquine Phosphate were exposed to stress conditions like acidic hydrolysis, basic hydrolysis, oxidative, photolytic, humidity and thermal conditions. Due to its simplicity, rapidness and high precision, the method was successfully applied to the estimation of Arterolane Maleate and Piperaquine Phosphate in combined dosage form.Key words: Arterolane Maleate, Piperaquine Phosphate, Method validation, Forced degradation.Plasmodium falciparum is responsible for half of these cases. Fixed dose combination of arterolane maleate (150 mg) and piperaquine phosphate (750 mg) has been recently approved by FDA as a once-a day therapy for three days for the treatment of acute, uncomplicated Plasmodium falciparum malaria 3 .