PP-009 Stability of intraveous injection of decitabine stored in polyethylene syringes

Abstract

BackgroundDecitabine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) de novo or secondary, according to the classification of the WHO, who are not candidates for conventional induction chemotherapy. There is a general recommendation about the maximum refrigerated (2–8°C) storage time for decitabine of 3 hours, but studies designed to explore stability beyond this period have not been conducted to date.PurposeTo evaluate the physical and chemical stability of decitabine stored in polyethylene syringes over a 24 hour period using proton nuclear magnetic resonance (1H-NMR) spectroscopy.Material and methodsCommercial solutions of decitabine (Dacogen) 5 mg/mL (50 mg in 10 mL of sterile water for injection) were packaged in polyethylene syringes. The syringe was stored in a refrigerator at 4°C±2°C for 24 hours in a digitalised temperature controlled chamber. The following physical parameters were monitored: turbidity and colour. Chemical stability was assessed by means of 1H-NMR spectroscopy. The 1H-NMR spectrum of a reference molecule was acquired. Spectroscopic signals were interpreted and assigned to the chemical structure of decitabine, and then consecutive spectra were acquired every hour during the 24 hour period. Signals obtained in these experiments were compared with those of the reference compound. All spectra were acquired using a Bruker Avance DRX 300 MHz spectrometer equipped with a 5 mm single axis z gradient quattro nucleus probe (Bruker Biospin GmbH, Rheinstetten, Germany).ResultsPhysical parameters monitored remained unchanged over the 24 hour period. During 7 hours, the chemical structure of the molecule was maintained unaltered, as demonstrated by 1H-NMR spectra identical to those of the reference compound. However, several signals corresponding to byproducts appeared in the sample stored at 4°C after 7 hours, proving that decitabine had suffered a degradation pathway.ConclusionDecitabine preserved its physical and chemical properties when stored packaged in polyethylene syringes for up to 7 hours at 4°C±2°C. This study comes into conflict with the information data sheet provided with decitabine, which recommends a maximum time of refrigerated (2–8°C) storage of 3 hours.References and/or acknowledgementsUniversity of Almería.No conflict of interest

LC–MS/MS Analysis on Infusion Bags and Filled Syringes of Decitabine: New Data on Physicochemical Stability of an Unstable Molecule

“…refrigeration time, the diluted solutions are stable for 1 h at room temperature before administration, which lasts for 1 h. In the literature, only two independent studies have already investigated decitabine stability in reconstituted and diluted solutions. 2,3 In Kim's study, analysis was performed by a validated stability-indicating reversed-phase high-performance liquid chromatography (HPLC) assay with photodiode array detection. The results report that reconstituted decitabine solution with cold sterile water is physicochemical stable in glass vials for 12 h at 2−8 °C and in 1 mL PC/PP (PC is polycarbonate, and PP is polypropylene) syringes for at least 28 days at −25 °C, while diluted decitabine solution in cold normal saline (NS) infusion bags stored under refrigeration is stable for approximately 24 h. In Fernaǹdez-Gineś's study, 5 mg/mL decitabine solutions in water for injection were packaged in polyethylene syringes and stored in a refrigerator at 4 ± 2 °C for 24 h. Chemical stability was assessed by means of 1 H NMR spectroscopy, by acquiring consecutive spectra every hour during a 24 h period.…”

Physicochemical Stability of Reconstituted Decitabine (Dacogen®) Solutions and Ready-to-Administer Infusion Bags when Stored Refrigerated or Frozen

“…In the latter case during subsequent administration at RT over 3 hours the decitabine concentration remained at or above 92 % [6]. By a literature research two poster presentations regarding the stability of Dacogen ® preparations were identified [7,8]. Patel studied the stability of reconstituted Dacogen ® powder stored at RT and diluted solutions (0.1 and 1.0 mg/mL) using either vehicle solutions stored at RT or prechilled (2-8°C) [8].…”

“…Patel studied the stability of reconstituted Dacogen ® powder stored at RT and diluted solutions (0.1 and 1.0 mg/mL) using either vehicle solutions stored at RT or prechilled (2-8°C) [8]. More recently the stability of reconstituted Dacogen ® powder stored refrigerated in polyethylene (PE) syringes and determined by a nuclear magnetic resonance ( 1 H-NMR) spectroscopy assay was presented [7]. The currently available stability information regarding Dacogen ® preparations is compiled in Table 1.…”