Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags

Eiden, Céline; Bekhtari, K.; Poujol, Sylvain; Malosse, Françoise; Pinguet, Frédèric

doi:10.2146/ajhp090039

Cited by 10 publications

(9 citation statements)

References 10 publications

(11 reference statements)

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“…Oxaliplatin was monitored and quantified at 255 nm while the degradation product was monitored at 205 nm. The main degradation products, diaquated oxaliplatin and oxalate, form slowly in 5% dextrose injection and have no significant absorbance at 255 nm 3. Oxaliplatin was separated isocratically on a C18 reverse phase analytical column (Agilent Zorbax SB C18 column (5 µm, 4.6×250 mm)) with the C18 pre-column at room temperature 8.…”

Section: Methodsmentioning

confidence: 99%

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Stability of lyophilised oxaliplatin formulation in polyolefin infusion bags containing 5% dextrose injection

et al. 2013

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Objective The in-use stability of lyophilised oxaliplatin and lactose formulation diluted in 5% dextrose injection was studied to assess the feasibility of preparing oxaliplatin solutions in advance in hospital pharmacy settings. The available in-use stability data of oxaliplatin solutions are based on infusions prepared with 5mg/mL concentrated solutions. Methods Oxaliplatin solutions of 0.5mg/mL (n=6), 0.7mg/mL (n=6) and 5mg/mL (n=6) were prepared using oxaliplatin 100mg powder and 100mL of 5% dextrose injection in polyolefin infusion bags. The samples were stored at 2-8 degrees C without light protection and were analysed at 1, 2, 4, 7, 14, 21 and 60days. The in-use stability was studied using the high-performance liquid chromatography stability indicating method. The solutions were checked for colour, particulate matter and pH. Results The mean concentrations of 0.5mg/mL and 0.7mg/mL oxaliplatin solutions decreased to less than 90%, within 7 and 14days, respectively, compared with the initial drug concentration in the solutions. The concentrated solution of 5mg/mL oxaliplatin was stable (over 90%) for at least 60days. The colour, clarity and pH remained unchanged throughout the storage period. Sterility and apirogenicity standards, as defined in the European Pharmacopoeia, were met. Conclusion Infusion solutions of oxaliplatin prepared with lyophilised oxaliplatin 100mg, 0.5mg/mL and 0.7mg/mL which were stored in polyolefin infusion bags, were chemically unstable within 7days and 14days, respectively, at 2-8 degrees C without light protection. The poor stability of the diluted solutions does not allow oxaliplatin to be prepared in advance and stored in pharmacy departments

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Section: Methodsmentioning

confidence: 99%

“…Incubation with 3% hydrogen peroxide (v/v) destroyed about 20% of intact oxaliplatin peak in 20 min and a new peak was observed, eluting at 2.4 min. In addition, degradation was forced by heating oxaliplatin 50 µg/mL and after 120 min more than 50% was destroyed3 (figure 2A–D).…”

Section: Methodsmentioning

confidence: 99%

Stability of lyophilised oxaliplatin formulation in polyolefin infusion bags containing 5% dextrose injection

et al. 2013

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“…Oxaliplatin diluted solutions in glucose 5% are chemically and physically stable also at relatively high concentrations up to 1.3 mg/mL, because its chemical structure remains unmodified and there are no aggregates of drug precipitate for a relatively long time [35,36].…”

Section: Oxaliplatin Chemistry and Pharmaceutical Propertiesmentioning

confidence: 99%

Oxaliplatin-Based Intra-arterial Chemotherapy in Colo-Rectal Cancer Liver Metastases: A Review from Pharmacology to Clinical Application

Ranieri

Laforgia

Ferraiuolo

et al. 2019

Cancers

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Liver metastases (LM) are often consequences of colo-rectal cancer (CRC)and the majority of patients have unresectable LM. Oxaliplatin-based intravenous chemotherapy represents the gold standard treatment for CRC. Intravenous oxaliplatin has several side effects i.e., nephrologic, hematologic and neurological toxicity. Moreover, hepatic arterial infusion (HAI) of antitumor drugs deeply modifies the treatment of LMCRC due to the knowledge that LM are perfused by the hepatic artery network, whereas healthy tissue is perfused by the portal vein. Therefore, oxaliplatin-based HAI becomes an interesting possibility to treat LMCRC. The aim of this review is to shed light on the important impact of the oxaliplatin-based chemotherapy from a non-conventional clinical point of view, considering that, being universally accepted its antitumor effect if administered intravenously, fragmentary information are known about its clinical applications and benefits deriving from intra-arterial administration in loco-regional chemotherapy.

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“…OX stability in aqueous solutions is explained by concentration effects and has been determined at no less than three years in D5W, forming association complexes at high concentrations that may affect uptake and molecular drug mechanisms (35). Its physicochemical stability in combination with D5W at concentrations >200 µg/ml (≙ ~500 µM) may further contribute to chemical inertness (36).…”

Section: Short-term Exposure To Drug Diluents Used In Hipec For 30/ 6mentioning

confidence: 99%

Short-term oxaliplatin exposure according to established hyperthermic intraperitoneal chemotherapy (HIPEC) protocols lacks effectivenessin vitroandex vivo

Löffler¹,

Seyfried²,

Burkard³

et al. 2019

Preprint

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Key Points: Oxaliplatin (OX)-containing solutions obtained during patient treatment with Hyperthermic intraperitoneal chemotherapy (HIPEC) unexpectedly showed low cytotoxicity in an impedance-based ex vivo cytotoxicity cell assay.  OX cytotoxicity under HIPEC conditions could be enhanced by extending drug exposure to one hour by an impedance-based ex vivo cytotoxicity cell assay.  HIPEC failed to show survival benefits in the randomized controlled PRODIGE 7 trial and was questioned in the aftermath.  Clinically relevant OX concentrations applied in conjunction with hyperthermia (42 °C) for 30 minutes, as used either at our own medical center or according to the PRODIGE 7 trial, proved predominantly ineffective, when used according to HIPEC routines in an impedance-based in vitro cytotoxicity cell assay.  Respective findings were corroborated in two different cell lines and by two established end-point assays, showing that 50 % cell death could not be reached by the same HIPEC treatment with OX, in contrast to continuous drug exposure.  As potentially relevant factor, the thickness of the exposed cell layer was identified, requiring at least ~100 µm penetration depth for our model to indicate effectiveness.  Additionally, we show relevant cell shrinkage by two drug diluents used either at our own medical center or according to the PRODIGE 7 trial, potentially associated with fluid shifts out of the cell and impaired drug effects.  Our own as well as recent findings by Ubink et al. (Br J Surg. 2019. doi: 10.1002/bjs.11206) support the notion that lacking effectiveness of OX HIPEC may explain the negative PRODIGE 7 trial results.

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Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags

Abstract: Oxaliplatin solutions diluted in 5% dextrose injection to 0.2 and 1.3 mg/mL were stable in PVC and PVC-free infusion bags for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure.

Cited by 10 publications

References 10 publications

Stability of lyophilised oxaliplatin formulation in polyolefin infusion bags containing 5% dextrose injection

Stability of lyophilised oxaliplatin formulation in polyolefin infusion bags containing 5% dextrose injection

Oxaliplatin-Based Intra-arterial Chemotherapy in Colo-Rectal Cancer Liver Metastases: A Review from Pharmacology to Clinical Application

Short-term oxaliplatin exposure according to established hyperthermic intraperitoneal chemotherapy (HIPEC) protocols lacks effectivenessin vitroandex vivo

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