Background Due to repetitive and tedious handling tasks, production of anticancer drugs for infusion is associated with a high risk of non-conformity. Thus, on-line quality control is necessary to improve the quality of preparation. Since the quantities produced are ever growing, very fast analytical methods of control are needed to minimise the delay before release.
Purpose A high-performance liquid chromatography method has been developed for quality control of vinca alkaloid infusion bags (vindesine, vincristine, vinorelbine and vinblastine).
Materials and Methods The separation was optimised by a Doehlert experimental design using a mixture of those 4 alkaloids. Chromatography was performed using Prostar Varian chromatographic equipment with a Photodiode array Detector. A short Polaris C18 column (3 µm, 50 mm × 4.6 mm) was used for all separations. The optimization varied 3 parameters: pH of the phosphate buffer 25 mM (7.0–7.6), flow rate of the mobile phase (0.7–1.3 mL.min−1) and proportion of acetonitrile (47–53%). 36 trials were necessary. The target response was the shortest run time giving a minimal resolution score of 1.5 for the most critical pair of peaks.
Results For vinorelbine, pH had a major effect on resolution. Optimal resolutions were obtained with a pH of 7.25. Then, the flow rate was set at 1.6 mL.min−1 with a mobile phase consisting of water-acetonitrile (47–53 v/v). Under these conditions, resolution was at least 1.6 with an analysis time less than 2.0 min. Retention times were 1.03, 1.27, 1.39 and 1.68 minutes for vindesine, vincristine, vinblastine and vinorelbine respectively. Methods were validated according to ICH criteria and are now routinely used without troubleshooting.
Conclusions This method allows in-line quality control of 4 vinca alkaloids in a very short time (less than 2 minutes) and constitutes a suitable and safe tool for chemotherapy preparation.
No conflict of interest.
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