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Multiobjective Optimization Approach in Evaluation of Chromatographic Behaviour of Zolpidem Tartrate and Its Degradation Products


Multiresponse optimization methodology in combination with experimental design was employed as a powerful technique for simultaneous optimization of input variables significant for evaluation of chromatographic behaviour of zolpidem tartrate, zolpacid, oxozolpidem, zolpyridine and zolpaldehyde towards various responses. In the first stage of the investigation fractional factorial design was used to decrease the number of variables that should be studied in detail. Among examined variables, pH of the mobile phase, percentage of organic modifier and buffer concentration showed to be statistically important and were consequently optimized with central composite design and Derringer’s desirability function. Four responses were considered, the retention factors of zolpacid and zolpaldehyde (the first and last peak) and the resolutions between critical peaks. Optimal conditions included Luna C18(2) analytical column (250 mm x 4.6 mm, 5 μm particle size), mobile phase consisted of methanol–10 mM ammonium acetate (68.4:31.6, v/v, pH 5.4) and column temperature of 35 °C. The flow rate of the mobile phase was 1 mL min−1 and the detection was performed at 254 nm. At the end, the method was successfully validated in accordance with ICH guideline and subsequently applied to the analysis of commercially available zolpidem tartrate tablets.

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Correspondence to Ljiljana Zivanovic.

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Malesevic, M., Zivanovic, L., Protic, A. et al. Multiobjective Optimization Approach in Evaluation of Chromatographic Behaviour of Zolpidem Tartrate and Its Degradation Products. Chromatographia 74, 197–208 (2011).

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  • Column liquid chromatography
  • Fractional factorial design
  • Central composite design
  • Derringer’s desirability function
  • Zolpidem tartrate