Background Gemcitabine ready to administer bags are frequently prepared in hospital pharmacies. Long-term stability for 84 days is published1 and dose-banding is already established at some hospitals. Little is known about the quality of different gemcitabine preparations.
Purpose Dose-banding has the advantage of quality control before use. However, with increasing storage time bags may lose quality due to degradation products with unknown effects.
Material and methods We performed a stability study with ready to administer bags prepared from gemcitabine hexal concentrate in the hospital pharmacy aseptic production unit and with ready to administer bags from gemcitabine SUN. Therefore, we determined the gemcitabine concentration and analysed the degradation products 2’-Desoxy-2’, 2’-difluoruridin (dFdU), O6,5’-Cyclo-5,6-dihydro-2’-desoxy-2’, 2’-difluoruridin and two diastereomeric alcohols during a storage time of up to 84 days using HPLC/DAD and LC-MS. In addition, we measured the pH of all preparations at the beginning and after 84 days. All methods were validated following the guidelines for the practical stability studies of anti-cancer drugs.2
Results We could confirm stability of 84 days in all gemcitabine preparations. In all bags the gemcitabine concentration was >95%. The content of all tested degradation products was significantly higher in the bags produced by the pharmacy in 0.9% NaCl. In these bags the content of the degradation products increased significantly during storage time, whereas in the ready to administer bag gemcitabine SUN only a small amount of dFdU was found. Here the signal of dFdU did not increase during a storage time over 13 months. The pH was about 7.0, whereas the pH in the bags diluted from gemcitabine concentrate was 2.7.
Conclusion We conclude that gemcitabine preparations with a more physiological pH have better quality. The advantages are longer stability with no increase of hydrolysis products over storage and the physiological pH may be more comfortable for the patient. To improve quality, we should consider changing the pH in the gemcitabine preparations in hospital pharmacies.
References and/or acknowledgements 1. http://www.esop.li/ejop.php
No conflict of interest.
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