Long-term stability of 10 mg/mL dobutamine injectable solutions in 5% dextrose and normal saline solution stored in polypropylene syringes and cyclic-oleofin-copolymer vials

Abstract

Objective

Dobutamine is an inotropic agent given to patients with low cardiac output or undergoing cardiac surgery in intensive care units. Routine clinical care protocols recommend a target dilution concentration of 10 mg/mL dobutamine from the 250 mg/20 mL commercial solution.

This study aimed to assess the 1-year stability of ready-to-use 10 mg/mL diluted dobutamine solutions. Two types of 50 mL conditioning, polypropylene (PP) syringes or cyclic-oleofin-copolymer (COC) vials and two diluents (5% dextrose (D5W) and normal saline (NS)) were tested.

Methods

Reversed-phase liquid chromatography coupled with an ultraviolet detection stability-indicating method was developed for dobutamine and validated according to selectivity, linearity, sensitivity, accuracy and precision. Chemical stability was considered to have been maintained if the measured concentrations were >90% of the initial concentration with no colour change. Physical stability was assessed through sterility tests, pH and osmolality monitoring, and subvisible particle counting. Containers were stored at −20±5°C, +5±3°C and +25±2°C with 60%±5% relative humidity in a dark, closed environment.

Results

According to this study, the physicochemical stability of 10 mg/mL dobutamine solutions prepared with D5W or NS is constant throughout a 365-day period when stored in COC vials, at all the aforementioned temperatures, whereas solutions in PP syringes required a refrigerated temperature and should not be administered after 21 days or 3 months when prepared with D5W or NS, respectively, or after 1 month at ambient temperature whatever the diluent.

Conclusion

Our results argue in favour of adopting the compounding of ready-to-use 10 mg/mL dobutamine solutions in COC vials in centralised intravenous additive services.

Introduction

Dobutamine is commonly used for patients experiencing cardiogenic or septic shocks, severe heart failure or undergoing cardiac surgery in intensive care units.¹ In France, injectable dobutamine solutions are available as 250 mg/20 mL packaged in glass vials.

Dobutamine monographs recommend intravenous administration by continuous infusion of the 250 mg/20 mL commercial solution diluted in either 5% dextrose (D5W) or normal saline solution (NS).² Routine care protocols recommend a target dilution concentration of 10 mg/mL. Previous studies have highlighted the risks incurred by this supplementary step when performed in the wards,^3–5 for example, high intervariability of dobutamine concentrations and risk of infection.^{6 7} Preparing ready-to-use 10 mg/mL injectable dobutamine solutions in centralised intravenous additive services (CIVAS) would eliminate this step and reduce risks.⁸ The stability of ready-to-use dobutamine solutions stored in plastic syringes has already been tested over several months, but the beyond-use-date (BUD) was never attained in those studies.^9–11 Other stability studies at various concentrations have been performed in polyvinyl chloride (PVC),^12–18 polyethylene (PE)¹⁸ or glass^{13 14 18} containers but only over short periods.

Ready-to-use vials in cyclic-oleofin-copolymer (COC) were specially designed to store injectable solutions:¹⁹ their mechanical properties^20–22 offer far greater storage propensity than plastic syringes. Recent studies support the claim that COC vials offer longer stability than polypropylene (PP) syringes for midazolam and norepinephrine ready-to-use solutions.^{21 23} Freezing has never been tested before as a storage method to gain longer stability for ready-to-use dobutamine solutions, nor has the long-term stability of 10 mg/mL dobutamine solution diluted in D5W and NS and stored in PP syringes or COC vials.

This study aimed to compare the stability of 10 mg/mL ready-to-use dobutamine solutions stored in either PP syringes or COC vials and diluted in either D5W or NS and at frozen (−20±5°C), refrigerated (+5°C±3°C) or ambient temperatures (+25°C±2°C with 60%±5% relative humidity).

Products

A 250 mg/20 mL hydrochloride dobutamine commercial solution (Panpharma, Luitre, France) was compounded with excipients such as sodium metabisulfite, hydrochloric acid (HCl) and water for injection. Hydrochloride dobutamine standard reference used for the validation step corresponded to the European Pharmacopoeia (EP) standard reference.

Products used to prepare the high-performance liquid chromatography (HPLC) mobile phase were 0.1 mM sodium acetate buffer, prepared with sodium acetate trihydrate (Merck, Fontenay-sous-Bois, France), acetic acid (VWR International, Fontenay-sous-Bois, France) and ultrapure water (using a PURELAB classic system; ELGA Véolia, Wasquehal, France), methanol (VWR International) and acetonitrile (VWR International).

Containers

COC vials were 50 mL AT-Closed vials (Batch: 0F10888156, Reference: VIA-500000; Aseptic Technologies, Gembloux, Belgium) and PP syringes were 50 mL luer-lock syringes (Batch: 1405208, Reference:300865; Plastipak, Becton Dickinson, Le Pont-de-Claix, France).

COC vials were designed especially for ready-to-use solutions²⁴ and filled via an M1 filling station (Aseptic Technologies) connected to a peristaltic pump (Flexicon Pump PF6, Watson Marlow, La Queue-les-Yvelines, France) as previously reported.²⁰

Chromatographic apparatus and conditions

Reversed-phase HPLC combined with an ultraviolet (UV) detector method measured the concentrations. The system (Agilent 1260 Infinity LC, Les Ulis, France) was equipped with a C18 column (Kinetex 5 µm, 150×4.6 mm; Phenomenex, Le Peck, France) maintained at +25°C. The wavelength of the UV detector (1260 MWD DEAAZ00942) was set at 280 nm according to the EP.²⁵ The mobile phase A/B/C 84/4/12% (v/v) with isocratic elution (1.8 mL/min) was prepared with 0.1 mM sodium acetate buffer (EP) [A], pH adjusted to 4.0, methanol [B] and acetonitrile [C]. ChemStation software (Openlabs CDS, version 01.05), was used for calibration, data acquisition and interpretation. Injection volume was 5 µL throughout the study. All reagents were of analytical grade.

Stock solutions

Quality controls were prepared by dissolving hydrochloride dobutamine EP standard reference (20 mg dobutamine hydrochloride CRS D2954000) in 10 mL graduated flasks with D5W (Viaflo, Baxter, France; Batch: 17CL006) or NS (Viaflo, Baxter, France; Batch: 17K06T4A) to obtain 2 mg/mL stock solutions. Calibration solutions were prepared by diluting stock solutions with D5W (Curve A) or NS (Curve B) to obtain eight different standard levels: 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.3, 1.5 mg/mL. The two calibration curves were traced in triplicate using these eight levels.

Forced degradation study

The selectivity of the method was based on comparing the chromatogram of the quality control dobutamine solution with the chromatograms obtained from the degradation study. The extreme conditions applied to the stock solution to obtain about 20% degradation of the initial amount of dobutamine were:²⁶

• Dilution in 37% HCl for 6 hours at 80°C and 7 days at 80°C for D5W and NS, respectively, then neutralised by NaOH

• Dilution in NaOH 0.05 M for 30 min at ambient temperature, then neutralised by HCl

• Dilution in 30% (v/v) H₂O₂ for 1 day at 60°C

• Storage in a heated chamber at 80°C for 14 days.

Degradation solutions were then diluted with D5W or NS to a 1 mg/mL target concentration prior to injection into the HPLC system.

Solution preparations

Injectable dobutamine solutions were prepared from the commercial 250 mg/20 mL (Batch: 70210) solutions by diluting with D5W or NS to obtain a 10 mg/mL dobutamine solution. These solutions were again diluted at 1/10 with D5W or NS before injection into the HPLC system.

Preparation and filling steps were executed in a controlled atmosphere (Laminar Flow MaxiSafe 2020; Thermo Scientific, Saint Herblain, France). PP syringes were manually prepared while the M1 filling station was used to fill and seal the caps on COC vials.²⁰

A total of 320 syringes and 640 vials were prepared for each dilution condition (D5W and NS).

Half of the vials were stored upright and the remaining half upside down to assess the role of the stopper in the potential loss of stability.

Each container was stored in a dark enclosure for 365 days.

Respecting the Société Française de Pharmacie Clinique (French Society of Clinical Pharmacy)/Groupe d’Evaluation et de Recherche sur la Protection en Atmosphère Contrôlée (Evaluation and Research Group on Protection in Controlled Atmosphere) (SFPC/GERPAC) and the International Conference of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guidelines,^{26 27} three storage conditions were tested for each container (upright, upside-down vials, syringes): −20°C±5°C, +5°C±3°C and 25°C±2°C with 60%±5% relative humidity). Defrosting conditions for frozen containers were fixed at 4 hours’ ambient temperature. A dye ingress test was successfully performed.²¹

Operating conditions for the stability study

Stability was assessed at days 0, 7, 14, 21 and months M1, M2, M3, M4, M5, M6, M7, M8, M9, M10, M11, M12. Each syringe or vial was used once per analysis.

Visual inspection and measurement of dobutamine concentration were carried out at each time point. Visual inspection analysis targets the formation of visible particles, transparency, and colouring of the solution. Dobutamine concentration was measured using the HPLC-UV-validated method. Chemical stability was assumed to be maintained if three criteria were met: no colour change, measured concentrations >90% of the initial concentration and no formation of toxic degradation product.

pH monitoring and a non-visible particulate contamination assay were performed in triplicate at the beginning of the study and every month until the end of the study or until the date of the assumed loss of physicochemical stability. pH values were measured using a Hanna HI 223 pH meter (HannaInstrument, Ann Arbor, MI, USA). A light obscuration spectrometer (APSS-2000; Particle Measuring Systems, Dourdan, France) was used for the non-visible particulate contamination assay. Preparations met the required criteria if the number of particles was within the limits set by the EP for 50 mL containers, namely a maximum of 6000 particles of sizes ≥10 µm/container and 600 particles of sizes ≥25 µm/container.²⁸

Sterility assay and osmolality measurements were made in triplicate for each condition at the beginning and at each reported BUD or at day 365 for solutions that had remained stable. The sterility test was conducted with the Müeller Hinton medium (CM0405 OXOID; Thermo Fisher Scientific, Basingstoke, UK) at +22°C/+33°C. This medium was validated according to the requirements of the EP.²⁹ Samples were filtrated via membranes with a 0.45 µm cellulose nitrate filter (Sartorius Stedim Biotech, Göttingen, Germany) and membranes were incubated in the medium for 14 days. The sterility test was passed if there was no growth of microorganisms. Osmolality was measured using a micro-osmometer (Model 210; Fiske Associates, Norwood, MA, USA).

Statistical tests

Calibration ranges were established by plotting the peak area obtained for the calibration solutions of dobutamine diluted in D5W or NS versus the concentration of dobutamine contained in these solutions. An analysis of variance (ANOVA), preceded by a Cochran test, was used to assess the linearity of our method. Concentration measures on samples prepared at the eight concentration levels of the two calibration ranges were made in triplicate to evaluate intraday precision and accuracy. These measures were repeated on three consecutive days to evaluate interday precision.

Accuracy and precision were calculated using the recovery factor and the coefficient of variation, respectively. Total error was calculated as the sum of relative bias and interday precision. The limit of acceptance was set at ±10%.²¹ pH values and osmolality results obtained at the beginning and end of the study were compared with a non-parametric Wilcoxon test (α=5%) for each condition and storage tested, using R software (Version 1.2.1335; R Foundation for Statistical Computing, Vienna, Austria).

Results

Forced degradation study

The chromatogram of the stock solution was compared with those obtained from the forced degradation study (figure 1).

Figure 1.

Representative chromatograms of (A.1/A.2) 10 mg/mL dobutamine reference solution diluted in normal saline solution (NS)/5% dextrose (D5W), (B.1/B.2) 10 mg/mL dobutamine solution in NS/D5W diluted in 0.05 M NaOH, (C.1/C.2) 10 mg/mL dobutamine solution in NS/D5W diluted in HCl 37% (v/v) at 80°C, (D.1/D.2) 10 mg/mL dobutamine solution in NS/D5W diluted in H₂O₂ 30% at 60°C.

Dobutamine was eluted at 2.3 min and 2.5 min when diluted in D5W or NS respectively. The peak at 1.1 min corresponds to the peak of D5W.

Degradation under basic conditions led to the formation of two products eluted at 2.7 and 2.9 min when diluted in D5W while the same two products were eluted at 2.8 and 3.2 min in NS. Degradation under acid conditions yielded one product eluted at either 6.3 min or 7.0 in D5W or NS. The other newly formed peaks corresponded to D5W degradation products.

Exposure to heat revealed no dobutamine degradation products, but some D5W degradation products. Exposure to oxidative conditions led to the apparition of many, not clearly separated peaks eluted between 0.9 and 1.8 min for D5W and between 0.9 and 1.6 min for NS. These peaks were associated with dobutamine and D5W degradation. The method was shown to be highly selective with no interference between the molecule and the degradation products.

HPLC validation assay for 0.5–1.5 mg/L range dobutamine solutions

The results for both calibration ranges are presented in table 1.

Table 1.

Calibration results

Parameters	Values for the calibration range diluted in D5W	Values for the calibration range diluted in NS
Range (mg/L)	0.5–1.5	0.5–1.5
Cochran test
Experimental value	0.26	0.24
Theoretical value (α=5%;8;6)	0.36	0.36
Correlation test (ANOVA)
Experimental value	18 968.72	5708.49
Theoretical value (α=5%;6;18)	4.07	4.07
Nonlinearity test (ANOVA)
Experimental value	1.67	0.47
Theoretical value (α=5%;1;18)	2.32	2.32
Regression coefficient
Slope	1980.08	1928.28
Intercept	−20.41	−37.44
Correlation coefficient	0.997	0.996
Limit of detection (mg/L)	0.032	0.054
Limit of quantification (mg/L)	0.064	0.108

D5W, 5% dextrose; NS, normal saline solution.

An excellent correlation between the ratio of peaks and dobutamine concentrations was demonstrated statistically. Linearity hypothesis was not rejected for either calibration range with a confidence level of 95%. Trueness and precision results are summarised in table 2.

Table 2.

Precision and accuracy calibration results of the high-performance liquid chromatographic method

Calibration	Concentration (mg/mL)	Relative bias (%)	Interday precision (%)	Total error (%)	Accuracy (%)
Dobutamine diluted in normal saline solution	0.5	0.66	3.67	4.33	100.66
	0.6	0.50	3.85	4.36	100.50
	0.7	0.39	3.95	4.33	100.39
	0.8	0.08	3.64	3.72	100.08
	0.9	2.10	5.33	7.43	97.90
	1.0	0.36	2.94	3.30	100.36
	1.3	0.03	3.09	3.12	100.03
	1.5	0.26	2.69	2.95	100.26
Dobutamine diluted in 5% dextrose in water	0.5	0.04	1.82	1.86	100.66
	0.6	0.12	2.13	2.25	100.50
	0.7	1.83	3.75	5.58	100.39
	0.8	2.65	2.76	5.42	100.08
	0.9	0.11	1.30	1.41	97.90
	1.0	0.28	1.92	2.20	100.36
	1.3	0.01	1.59	1.60	100.03
	1.5	0.05	1.40	1.45	100.26

Accuracy and total error scores did not exceed the tolerated limits, which are [90%–110%] and <10%, respectively (table 2). The results of the validation assay prove the reliability of our method based on linearity, selectivity, sensitivity, accuracy and precision.

Physical stability of dobutamine

Solutions freshly prepared were transparent with no visible particles. The initial physical parameters of the stability solutions are presented in online supplemental table S1.

Colour modification

When stored in COC vials, the solutions remained clear and free from visible particles throughout the study. Faint colouring was observed in solutions stored in COC vials at ambient temperature but was considered too slight to justify the discontinuation of the study (online supplemental figure S1A). No colouring or visible particles were observed in PP syringes stored at refrigerated or frozen temperatures throughout the study. However, colour modification was observed from the first month (M1) for solutions prepared in D5W or NS and stored at ambient temperature in PP syringes. From the second month (M2), this colouring became absolute, leading to the interruption of the study in these test conditions. This evolution is presented in online supplemental figure S1B–D.

Non-visible particulate contamination assay

Results are summarised in online supplemental tables 2 and 3.

For dobutamine solutions prepared with D5W, non-visible particulate contamination was maintained within the EP thresholds whatever the storage temperature in both containers at refrigerated temperature. Particles ≥10 µm and ≥25 µm exceeded the recommended limit from the sixth month (M6) and third month (M3), respectively, for solutions stored in PP syringes at ambient room temperature. Finally, for PP syringes at frozen temperature, the first atypical value for ≥10 µm particles was measured after the first month (M1) and continued from M6 till the end of the study whereas no such value was measured for ≥25 µm particles.

For dobutamine solutions prepared with NS, the results obtained for the non-visible particle assay stored in COC vials, whatever the storage temperature, showed no deviations from EP thresholds. The results were identical for the 10 mg/mL dobutamine solutions prepared with NS and stored in PP syringes at refrigerated temperature. However, both particles ≥10 µm and ≥25 µm exceeded the recommended limit from the second month (M2) for solutions stored in PP syringes at ambient temperature. For dobutamine solutions prepared with NS and stored at frozen temperature, the recommended thresholds were exceeded from the fourth (M4) and sixth (M6) months, for particles ≥10 µm and ≥25 µm, respectively.

pH monitoring and osmolality assay

The evolution of pH values is described in figure 2. The results of the osmolality assay are presented in table 3.

Figure 2.

Evolution of pH values of 10 mg/mL dobutamine solutions diluted in normal saline solution or 5% dextrose and stored either in cyclic-oleofin-copolymer vials or polypropylene syringes stored at ambient (+25°C/60% relative humidity), refrigerated (+5°C) or frozen (−20°C) temperatures, throughout the 12-month study period. COC, cyclic-oleofin-copolymer; D5W, 5% dextrose; NS, normal saline solution; PP, polypropylene; RH, relative humidity.

Table 3.

Osmolality results obtained at the end of the stability study of the 10 mg/mL dobutamine solution diluted in 5% dextrose or normal saline solution and stored in either cyclic-oleofin-copolymer vials or polypropylene syringes stored at ambient (+25°C/60% relative humidity), refrigerated (+5°C) or frozen (−20°C) temperatures, throughout the 12-month study period.

Condition	Diluent	D5W			NS
	Storage temperature	+25°C/60% RH	+5°C	−20°C	+25°C/60% RH	+5°C	−20°C
Upright COC vials	Time of measurement	M12	M12	M12	M12	M12	M12
	Osmolality values (mOsmol/kg)	122±1	121±1	120±0	121±0	120±0	119±0
Upside-down COC vials	Time of measurement	M12	M12	M12	M12	M12	M12
	Osmolality values (mOsmol/kg)	121±0	121±1	120±1	121±0	120±1	120±1
PP syringes	Time of measurement	M2*	M12	M1*	M2*	M12	M4*
	Osmolality values (mOsmol/kg)	134±11	120±1	124±8	128±8	120±1	121±4

*The study was stopped once the stability of the solution had deteriorated.

COC, cyclic-oleofin-copolymer; D5W, 5% dextrose; M, month; NS, normal saline solution; PP, polypropylene; RH, relative humidity.

These results show no significant difference between pH values (n=3, p value ≥0.07) and osmolality values (n=3, p value >0.06), measured at the beginning and end of the study in all comparative conditions.

Chemical stability

The initial dobutamine concentrations were 10.54±0.31 mg/mL (n=3) and 10.18±0.15 mg/L (n=3) when diluted in D5W and NS, respectively. figure 3 shows that chemical stability was maintained over the 365-day study period for dobutamine solutions, whatever the diluent (D5W or NS) in COC vials and whatever the storage temperature condition, and in PP syringes at refrigerated or frozen temperature. Chemical stability was lost from M9 for solutions prepared with either D5W or NS stored in PP syringes at room temperature.

Figure 3.

Chemical stability of 10 mg/mL dobutamine solutions diluted in normal saline solution or 5% dextrose and stored in either cyclic-oleofin-copolymer vials or polypropylene syringes at ambient (+25°C/60% relative humidity), refrigerated (+5°C) or frozen (−20°C) temperatures. COC, cyclic-oleofin-copolymer; D5W, 5% dextrose; NS, normal saline solution; PP, polypropylene; RH, relative humidity.

Sterility assay

Sterility was maintained throughout the 12-month study for every solution stored in COC vials whatever the storage condition and diluent, for solutions stored in PP syringes at refrigerated temperature and up to the BUD for the other conditions.

Discussion

The physicochemical stability of 10mg/mL dobutamine solutions prepared with D5W or NS was maintained throughout a 365-day period, when stored in COC-vials, at all temperature conditions tested(−20±5°C,+5±3°C and +25±2°C with 60%±5% relative humidity); and in PP-syringes but only when refrigerated. 10mg/mL dobutamine solutions stored after 1 month at ambient temperature when prepared with either D5W or NS. The rapid exceeding of subvisible particle contamination limits with PP syringes advocates limiting routine frozen storage of diluted intravenous dobutamine solutions. The faint colouring observed in solutions stored in COC vials at ambient temperature contributes to favouring storage at +5°C.

This is the first study to explore the stability of diluted dobutamine over a 1-year period.

Previous studies have evaluated the stability of diluted dobutamine, either in D5W,9 11–18 30 or NS,^12–18 protected from light11 13 15 18 30 or not,9 10 14 17 exposed to various storage temperatures (ambient,9 11–14 16–18 30+35°C¹² or refrigerated10–13 15 16 18 30), compounded in glass,^{13 14 18} polyvinyl chloride (PVC),^12–18 polyethylene (PE)¹⁸ or PP^{9 11} containers. Some assessed the chemical stability of dobutamine solutions in PP syringes at ambient and refrigerated temperatures without reaching the BUD,^{9 11} but evaluation was over a shorter period (42 days maximum).

An innovative point in this study was particle contamination counting, not performed in previous studies.9 11–14 30 Subvisible particle contamination should be considered in stability studies as it is responsible for clinical consequences especially in critically ill patients receiving multidrug infusions.^{31 32}

Some COC vials (with D5W, n=2/with NS, n=1) cracked during storage when frozen. This phenomenon was linked to dobutamine crystallisation (crystals found in cracks and analysed by HPLC-UV). Dobutamine concentrations measured in the cracked vials revealed an average loss of 4% of the initial concentration. The manufacturer explained that the maximal filling volume recommended for 50 mL COC vials was 45 mL before freezing because of expansion of the diluent, and confirmed that COC vials can be submitted to temperatures as low as −50°C.³³ This cracking phenomenon was not observed in previous studies with cefuroxime, midazolam or norepinephrine but requires further investigation. Our study was pursued on uncracked vials. As for syringes, the above phenomenon did not occur in our study. However, Kirk et al reported a contraction of the PP syringe plunger during cooling, resulting in leakage of the solution past the plunger.³⁴ We did not experience this phenomenon either in this or previous studies.

Data reporting the chemical stability of dobutamine submitted to extreme conditions is controversial. A recent article reported that dobutamine was stable in basic and thermal conditions but sensitive to degradation in acidic conditions,¹² while another declared the opposite.¹¹ Our degradation study suggests that dobutamine was sensitive to acidic, basic and oxidative conditions but not to heat. However, the impact of heat on dobutamine degradation is highly probable as colouring was observed but does not correspond to the appearance of any peak in the chromatograms. The limit of our HPLC-UV detection method was the undetectability of the dobutamine degradation product obtained from its thermal degradation. Regardless of extreme conditions leading to dobutamine degradation, the degradation mechanism is considered to be a free radical-mediated mechanism leading to the formation of dark-coloured polymers.³⁵

The 10 mg/mL dobutamine solutions stored in PP syringes in the dark turned brown before the end of the 12-month study period, showing a susceptibility to heat in this type of container.

There is no evidence that the coloured degradation products of dobutamine are not toxic. Colouring may indicate limited stability even though the drug concentration remained within acceptance limits. This finding is similar to that of other authors.^{11 13}

Our results concur with previous studies affirming longer stability in COC vials than in PP syringes;^20–23 COC vials also showed their superiority over PP syringes as regards subvisible particle contamination. The similarity of the results whatever the position of the vial during storage suggests that contact with the stopper has no impact on the stability of the 10 mg/mL dobutamine solution. This complies with the declared properties of COC vials meeting the criteria requirements for pharmaceutical primary containers.²⁴

Our method is adapted to CIVAS, as are many previously published methods combining reversed-phase HPLC and UV detection.^10–14

Finally, plastic syringes used to pose a problem for compounding as they were not made for storing drugs but this situation has recently been resolved as Becton Dickinson claims that their syringes now conform to drug storage.²¹

Conclusions

Our results advocate adopting the compounding of ready-to-use 10 mg/mL dobutamine solutions in COC vials in CIVAS and their storage at refrigerated temperature. Frozen storage is not recommended for COC vials because of the risk of cracking. PP syringes offer acceptable 1-year shelf-life stability for 10 mg/mL dobutamine solutions when refrigerated.

What this paper adds.

What is already known on this subject

• Medication errors linked to the dilution step can be avoided by preparing ready-to-use injectable solutions in hospital pharmacies.

• As dobutamine is a high-risk medication, a dilution error may be deleterious for critically ill patients.

What this study adds

• The stability of ready-to-use 10 mg/mL dobutamine solution depends on storage temperature, diluent and type of container.

• The stability of ready-to-use 10 mg/mL dobutamine solutions diluted in 5% dextrose in water (D5W) and 0.9% NaCl was maintained for 12 months in cyclic-oleofin-copolymer (COC) vials at −20°C, +5°C and +25°C and in polypropylene (PP) syringes at +5°C.

• In PP syringes at −20°C and +25°C, the beyond-use delay was shorter: 21 days (D5W) and 3 months (0.9% NaCl) at −20°C, and 1 month at +25°C.

Data availability statement

Data are available in a public, open access repository: Gilliot, Sixtine; Henry, Héloïse; Carta, Natacha; Genay, Stéphanie; Barthélémy, Christine; Décaudin, Bertrand; Odou, Pascal (2020), “Long-term stability of 10 mg/mL dobutamine injectable solutions dataset”, Mendeley Data, V1, doi: 10.17632/cxs7y94kj8.1.

Ethics statements

Patient consent for publication

Not required.