• Jérôme Vial, Mélanie Cohen, Patrick Sassiat, and Didier Thiébaut.
• Laboratoire Environnement et Chimie Analytique, Paris, France. jerome.vial@espci.fr
• Curr Med Res Opin. 2008 Jul 1; 24 (7): 2019-33.

IntroductionThe aim of this study was to evaluate the quality of 31 commercially available generic formulations of docetaxel purchased in 14 countries by comparing their docetaxel content, impurity levels and pH versus those of the proprietary product Taxotere (Tx).Research Design And MethodsGeneric formulations were purchased in 14 countries in Asia, Africa, the Middle East and Latin America. Levels of docetaxel and impurities (chromatographic peaks above 0.05%) were obtained for each sample using reverse-phase liquid chromatography with ultraviolet detection. The pH of aqueous solutions of generic docetaxel formulations and Tx was also measured. A global evaluation of quality was conducted on each product using a multicriteria desirability analysis based on standards defined by the International Conference on Harmonisation guidelines and the US Pharmacopeia paclitaxel injection monograph.ResultsMost generic formulations contained a lower than expected amount of docetaxel and/or a high level of impurities: 21 generic docetaxel formulations had an average mass of docetaxel that was <90% of the expected mass and 23 generic docetaxel formulations had a total impurity content of >3.0%, almost twice the level of impurities in Tx 20 mg. In total, 33 impurities not present in Tx were detected in the generic samples. Desirability analysis demonstrated that none of the generic docetaxel formulations had composition characteristics similar to those of Tx.ConclusionsThis study demonstrated that from an analytical point of view, 90% of the generic docetaxel formulations evaluated contained insufficient active drug, high levels of impurities or both. This has the potential to affect both efficacy and safety of the drug.

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