Stability of oxaliplatin in chloride-containing carrier solutions used in hyperthermic intraperitoneal chemotherapy

A. M. Mehta*, J. M. Van den Hoven, H. Rosing, M. J. X. Hillebrand, B. Nuijen, A. D. R. Huitema, J. H. Beijnen, V. J. Verwaal

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Abstrakt

Purpose: Oxaliplatin is increasingly becoming the chemotherapeutic drug of choice for the treatment of peritoneal malignancies using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS HIPEC). Oxaliplatin is unstable in chloride-containing media, resulting in the use of 5% dextrose as the carrier solution in these procedures. Exposure of the peritoneum to 5% dextrose during perfusion times varying from 30 min to 90 min is associated with serious hyperglycemias and electrolyte disturbances. This can result in significant postoperative morbidity and mortality. In order to find out whether safer, chloride-containing carrier solutions can be used, we report the results of in-vitro analysis of oxaliplatin stability in both chloride-containing and choride-deficient carrier solutions and discuss the implications for oxaliplatin-based CRS HIPEC procedures.

Methods: 5 mg of oxaliplatin was added to 50 mL of various carrier solutions at 42 C: 5% dextrose, 0.9% sodium chloride, Ringer lactate, Dianeal (R) PD4 glucose 1.36% solution for peritoneal dialysis and 0.14 M sterile phosphate buffer pH 7.4. Samples were collected at standardized intervals and oxaliplatin concentration was determined using a stability indicating high-performance liquid chromatographic method, coupled to an UV detector (HPLC UV); oxaliplatin degradation products were identified using HPLC-mass spectometry.

Results: In 5% dextrose, oxaliplatin concentration remained stable over a 2-hour period. Increasing chloride concentrations were associated with increasing degradation rates; however, this degradation was limited to

Conclusions: The use of chloride-containing carrier solutions for oxaliplatin does not relevantly affect its concentrations under the tested in-vitro conditions. Chloride seems to promote formation of the active cytotoxic drug form of oxaliplatin and therefore could enhance its cytotoxic effect. These data show that more physiological, chloride-containing carrier solutions can be used safely and effectively as a medium for oxaliplatin in CRS HIPEC procedures. (C) 2014 Elsevier B.V. All rights reserved.

OriginalsprogEngelsk
TidsskriftInternational Journal of Pharmaceutics
Vol/bind479
Sider (fra-til)23-27
Antal sider5
ISSN0378-5173
DOI
StatusUdgivet - 1. feb. 2015
Udgivet eksterntJa

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