Stability of celecoxib oral suspension

Background:

Celecoxib is a selective cyclo-oxygenase 2 inhibitor that relieves pain without affecting platelet function, causing gastrointestinal toxic effects, or increasing the risk of bleeding.

Objectives:

To develop a suspension formulation for oral celecoxib and to determine its physical and chemical stability when packaged in amber polyvinyl chloride (PVC) bottles and stored with refrigeration (5°C) and at room temperature (23°C).

Methods:

The contents of celecoxib capsules were used to prepare a single suspension, with Ora-Blend used as the suspending and flavouring agent. The suspension (10 mg/mL) was then packaged in amber PVC bottles and stored at either 5°C or 23°C. Samples were collected on days 0, 7, 14, 21, 27, 56, and 93. Chemical stability was determined using a validated stability-indicating high-performance liquid chromatography method. At each sampling time, the suspensions were checked visually for changes in appearance (i.e., colour, layering, caking, and ease of resuspension), odour, and pH.

Results:

All of the suspensions were stable for at least 93 days, regardless of storage conditions. There were no apparent changes in physical appearance, nor were there any substantial changes in odour or pH.

Conclusions:

Suspensions of celecoxib (10 mg/mL in Ora-Blend) packaged in amber PVC bottles were stable for up to 93 days when stored at 5°C or 23°C. A 3-month expiry date has been established for this oral suspension on the basis of physical compatibility and chemical stability.     

Stability of pantoprazole sodium in glass vials, polyvinyl chloride minibags, and polypropylene syringes

Background:

Pantoprazole sodium, a proton-pump inhibitor, is approved for the short-term treatment of several types of ulcer, Zollinger–Ellison syndrome, and gastroesophageal reflux disease.

Objective:

To determine the physical compatibility and chemical stability of ethylenediaminetetra-acetic acid (EDTA)–free pantoprazole in glass vials, polypropylene syringes, and polyvinylchloride (PVC) minibags, after storage at 2°C to 8°C with protection from light or at 20°C to 25°C with exposure to light.

Methods:

Solutions of pantoprazole 4 mg/mL reconstituted in 0.9% sodium chloride (normal saline [NS]) were stored in glass vials at 20°C to 25°C. Similar solutions were transferred to polypropylene syringes and stored at 2°C to 8°C. Stock solution was further diluted, in 5% dextrose in water (D5W) or NS, to 0.4 or 0.8 mg/mL, and samples were then packaged in PVC minibags for storage at 2°C to 8°C or at 20°C to 25°C. Samples collected on days 0, 2, 3, 7, 14, 21, and 28 were analyzed in duplicate with a stability-indicating high-performance liquid chromatography assay.

Results:

Pantoprazole 4 mg/mL was stable (i.e., retained at least 90% of initial concentration) for 3 days when stored in glass vials at 20°C to 25°C or for 28 days when stored in polypropylene syringes at 2°C to 8°C. Pantoprazole 0.4 mg/mL diluted in D5W and stored in PVC minibags was stable for 2 days at 20°C to 25°C or for 14 days at 2°C to 8°C. At 0.8 mg/mL, pantoprazole in D5W was stable for 3 days at 20°C to 25°C or 28 days at 2°C to 8°C. Pantoprazole diluted to either 0.4 or 0.8 mg/mL in NS and stored in PVC minibags was stable for 3 days at 20°C to 25°C or 28 days at 2°C to 8°C.

Conclusions:

The present study confirmed or extended previously reported expiry dates for pantoprazole sodium packaged in glass vials, polypropylene syringes, and PVC minibags.     

Stability of ciprofloxacin in polyvinylchloride minibags

Background:

Ciprofloxacin is a fluoroquinolone antibiotic used to treat infections caused by both gram-positive and gram-negative organisms.

Objective:

To determine the physical and chemical stability of ciprofloxacin diluted in 5% dextrose in water (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored in polyvinylchloride (PVC) minibags at various temperatures.

Methods:

Solutions of ciprofloxacin (1 and 2 mg/mL) were prepared by diluting a commercially available concentrate (10 mg/mL) with either D5W or NS. The prepared solutions were then packaged in PVC mini-bags. Three minibags of each concentration–diluent combination were stored at 2°C to 8°C with protection from light, at 21°C to 24°C with exposure to light, and at 29°C to 31°C with protection from light. Samples were collected from each minibag on days 0, 7, 14, and 30 and then analyzed. Colour, clarity, and pH were monitored when the samples were collected. On each day of analysis, the samples were accurately diluted before duplicate analysis with a stability-indicating high-performance liquid chromatography assay. A solution was considered stable if the concentration remained above 90% of the initial values.

Results:

There were no changes in the physical characteristics of any of the solutions. At both concentrations (1 and 2 mg/mL), the ciprofloxacin solutions prepared in D5W remained above 93.9% of the initial concentration over the 30-day study period under all 3 storage conditions. Similarly, at both concentrations, solutions diluted in NS remained above 95.9% of the initial concentration over the 30-day study period under all 3 storage conditions.

Conclusions:

Ciprofloxacin prepared in either D5W or NS and stored in PVC minibags was stable for 30 days under 3 separate storage conditions: 2°C to 8°C with protection from light, 21°C to 24°C with exposure to light, and 29°C to 31°C with protection from light.     

Buffered lidocaine hydrochloride solution with and without epinephrine: stability in polypropylene syringes

Background:

Pain associated with infiltrating the skin with lidocaine can be reduced by buffering the solution with sodium bicarbonate.

Objectives:

To determine the physical compatibility and chemical stability of lidocaine hydrochloride solution buffered with 8.4% sodium bicarbonate, with and without epinephrine, packaged in polypropylene syringes and stored at 5°C with protection from light.

Methods:

Lidocaine solutions (1% and 2%), with and without epinephrine 1:100 000, were diluted 10:1 with 8.4% sodium bicarbonate, packaged in 3-mL polypropylene syringes, and stored at 5°C (range 3°C to 8°C). On each of days 0, 3, 7, 10, 14, 17, 21, 24, and 28, the contents of 3 syringes for each solution of lidocaine combined with epinephrine were collected separately in glass vials and frozen at −70°C for subsequent analysis. In addition, on days 0, 7, 14, 21, and 28, the contents of 3 syringes for each lidocaine solution without epinephrine were collected separately in glass vials and frozen at −70°C for subsequent analysis. Chemical stability was determined with a validated, stability-indicating high-performance liquid chromatography method. Changes in colour, clarity, and pH were used to determine physical compatibility of the solutions.

Results:

All buffered lidocaine solutions containing epinephrine (1:100 000) retained at least 93.3% of the original concentration of epinephrine and 97.5% of the lidocaine concentration for 7 days when stored at 5°C with protection from light. In contrast, the epinephrine-free solutions retained at least 94.7% of the initial concentration of lidocaine for the duration of the study (28 days). All samples remained clear, colourless, and free of precipitate throughout the study, and there were no significant changes in pH.

Conclusion:

Extemporaneously prepared buffered lidocaine (1% and 2%) packaged in polypropylene syringes remained stable for up to 28 days when properly refrigerated with protection from light. A 7-day expiry date was established for buffered lidocaine solutions containing epinephrine, packaged in polypropylene syringes, and stored with refrigeration and protection from light.     

Stability of commonly used antibiotic solutions in an elastomeric infusion device

Background:

The Accufuser silicone-based elastomeric infusion device has recently been approved for the Canadian market.

Objective:

To evaluate the stability of 5 antibiotics (cefazolin, ceftazidime, ceftriaxone, clindamycin, and vancomycin) in either 5% dextrose in water (D5W) or 0.9% sodium chloride in water (NS) after storage in Accufuser disposable silicone balloon infusers.

Methods:

The study drugs were reconstituted, according to the manufacturers’ directions, in polyvinyl chloride minibags with either D5W or NS, at 2 different concentrations. The resulting solutions were transferred to disposable silicone balloon infusers for storage at 4°C or at room temperature (23°C). The concentration of each drug in each solution was determined by validated stability-indicating liquid chromatographic methods after storage for 14 to 31 days.

Results:

Solutions of ceftriaxone in either diluent retained more than 95.2% of the initial concentration for 2 days at room temperature and more than 91.6% of the initial concentration for 14 days at 4°C. Solutions of cefazolin in D5W or NS retained more than 90% of the initial concentration for at least 3 days at room temperature and for at least 26 days at 4°C. Solutions of ceftazidime in D5W or NS retained more than 90% of the initial concentration for only 1 day when stored at room temperature and for at least 4 days at 4°C. Solutions of clindamycin or vancomycin in D5W or NS retained 90% of the initial concentration for at least 7.5 days at room temperature and at least 90% of the initial concentration for at least 27.8 days at 4°C.

Conclusions:

Previously reported expiration dates for solutions stored in elastomeric infusion devices were not based on 95% confidence intervals and were often longer than expiration dates determined from the studies reported here, which are based on 95% confidence intervals. Comparison of the observed concentrations remaining between previously published studies and the studies reported here indicates that the Accufuser elastomeric infusion device did not adversely affect the stability of these drugs.     

Stability of cefazolin sodium in polypropylene syringes and polyvinylchloride minibags

Background:

Cefazolin is a semisynthetic penicillin derivative with a narrow spectrum of activity covering some gram-positive organisms and a few gram-negative aerobic bacteria.

Objective:

To determine the physical and chemical stability of cefazolin sodium reconstituted with sterile water for injection and stored in polypropylene syringes or diluted with either 5% dextrose in water (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored in polyvinylchloride (PVC) minibags.

Methods:

Reconstituted solutions of cefazolin (100 or 200 mg/mL) were packaged in polypropylene syringes. More dilute solutions (20 or 40 mg/mL) were prepared in D5W or NS and packaged in PVC minibags. For each concentration–diluent–container combination, 3 containers were designated for each day of analysis (days 7, 14, 21, and 30). Containers were stored under refrigeration (5°C) with protection from light until the designated day of analysis, at which time one 5-mL sample was collected from each the designated container. The designated containers were then stored at room temperature (21°C to 25°C) with exposure to light for an additional 72 h, and additional samples were drawn. The samples were assayed using a validated, stability-indicating high-performance liquid chromatography method. The colour and clarity of the solutions, as well as their pH, were also monitored on each sampling day.

Results:

All samples remained clear for the duration of the study; they had a slight yellow colour that darkened over time, and there was an increase in pH. Solutions diluted with sterile water for injection and stored in polypropylene syringes retained at least 94.5% of the initial concentration after 30 days of refrigerated storage and at least 92.1% after an additional 72 h at room temperature with exposure to light. Samples diluted in D5W or NS and stored in PVC minibags retained at least 95.8% of the initial concentration after 30 days of refrigerated storage and at least 91.8% after an additional 72 h at room temperature with exposure to light.

Conclusions:

Cefazolin at various concentrations stored in polypropylene syringes or PVC minibags was stable for up to 30 days with storage at 5°C with protection from light, followed by an additional 72 h at 21°C to 25°C with exposure to light.     

Extended stability of pantoprazole for injection in 0.9% sodium chloride or 5% dextrose at 4°c and 23°c

Background:

The pantoprazole product available in Canada for IV administration has recently been reformulated to include ethylenediaminetetra-acetic acid (EDTA). The purpose of this study was to determine if the chemical stability of pantoprazole for injection containing EDTA (PANTO IV), admixed in polyvinyl chloride (PVC) minibags at concentrations of 0.16 mg/mL and 0.80 mg/mL in 5% dextrose in water (D5W) or 0.9% sodium chloride for injection (normal saline [NS]) and stored at 4°C or 23°C, could be extended beyond the manufacturer’s expiry period of 24 hours.

Methods:

Sodium pantoprazole was reconstituted in NS or D5W, and 32 PVC minibags were prepared, 16 containing pantoprazole at a nominal concentration of 0.16 mg/mL (8 in NS, 8 in D5W) and 16 containing pantoprazole at a nominal concentration of 0.80 mg/mL (8 in NS, 8 in D5W). Half of the minibags for each diluent–concentration combination were stored at 4°C and half at room temperature (23°C). The concentration of pantoprazole in each minibag was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 4, 7, 9, 11, 14, and 21.

Results:

Analysis of variance revealed differences in the percentage of drug remaining in relation to temperature (p < 0.001), study day (p = 0.001), concentration (p = 0.007), and diluent (p = 0.008).

Conclusions:

Solutions of pantoprazole in D5W with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for a maximum of 11 days at 4°C plus an additional 6 h at 23°C. The saline solutions degraded more slowly, and pantoprazole admixtures in NS with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for 20 days at 4°C plus an additional 6 h at 23°C. Under these conditions, more than 90% of the initial concentration will remain (with 95% confidence).     

Stability of aseptically prepared tazocin solutions in polyvinyl chloride bags

Background:

Tazocin, a mixture of piperacillin and tazobactam, has recently been reformulated to include edetate disodium (EDTA) and citric acid. Since the introduction of this new formulation, there have been no studies of stability in polyvinylchloride (PVC) bags.

Objective:

To complete a physical compatibility and chemical stability study of the new formulation of Tazocin, prepared at 2 concentrations in each of 2 diluents and stored in PVC bags.

Methods:

Tazocin, at 22.5 or 90 mg/mL, was compounded in dextrose 5% in water (D5W) or 0.9% sodium chloride (normal saline [NS]) in PVC bags. The bags were stored at 5°C with protection from light for 14, 21, or 28 days, followed in each case by storage at 23°C with exposure to light for 72 h. Triplicate samples collected at each of the 7 time points were analyzed in duplicate using a stability-indicating high-performance liquid chromatography method. Physical compatibility was determined by monitoring the solutions for changes in colour, clarity, and pH.

Results:

The amount of each drug remaining for each concentration in each diluent was above 95% of the initial concentration after storage at 5°C with protection from light and above 94% of the initial concentration after an additional 72 h at 23°C with exposure to light. The pH of the solutions changed only slightly over the course of the study, and all solutions remained clear and colourless.

Conclusions:

Tazocin solutions at 22.5 and 90 mg/mL, prepared in PVC bags of either D5W or NS, were chemically stable after storage for up to 28 days at 5°C with protection from light followed by 72 h at 23°C with exposure to light.     

Stability of Ibuprofen solutions in normal saline or 5% dextrose in water

Background:

A shortage of the standard medication for treatment of patent ductus arteriosus has necessitated use of parenteral ibuprofen, which is equally efficacious for this indication. The beyond-use date recommended by the manufacturer is very short and has implications for resource allocation and wastage.

Objective:

To evaluate the stability of ibuprofen (undiluted or diluted in either 0.9% sodium chloride [normal saline; NS] or 5% dextrose in water [D5W]) with storage for up to 21 days under refrigeration or at room temperature in glass vials or polypropylene syringes.

Methods:

Six glass vials, each containing undiluted ibuprofen (5 mg/mL), were prepared. In addition, ibuprofen was diluted to 2.5 mg/mL in NS or D5W, and 6 syringes were prepared for each diluent (total of 12 syringes). Finally, 6 extension tubes were each primed with 1 mL of ibuprofen (duplicates of undiluted solution and solutions diluted to 2.5 mg/mL in NS or D5W). Half of the vials, syringes, and tubes were stored under refrigeration (4°C) and the other half at room temperature (23°C). The concentration of ibuprofen was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 3, 6, 8, 10, 13, 17, and 21 for samples stored in vials and syringes, or at time 0, 6, 24, and 30 h for samples stored in tubes.

Results:

Analysis of variance showed differences in the percentage of ibuprofen remaining due to study day (p < 0.001) and diluent (p < 0.005), but no differences due to concentration (p = 0.06) or temperature (p = 0.12). All solutions of ibuprofen were stable throughout the study period, retaining at least 90% of their initial concentration.

Conclusions:

Undiluted ibuprofen (5 mg/mL) stored in glass vials and ibuprofen diluted to 2.5 mg/mL with either NS or D5W and stored in polypropylene syringes will retain more than 92% of its initial concentration with storage for up to 14 days at 4°C. A beyond-use date of 14 days would allow for up to 24 h storage at 23°C during this 14-day period. Storage of ibuprofen solutions in extension tubing should not exceed 29 h at 4°C or 17 h at 23°C. Beyond-use dates should be applied only after consideration of US Pharmacopeia Revised General Chapter <797> guidelines for compounding of sterile preparations.     

Stability of norepinephrine solutions in normal saline and 5% dextrose in water

Background:

Most previous stability studies for norepinephrine have reported the percentage of drug remaining in IV solutions after only 24 h. No previously published study has evaluated the effect of light on the stability of this drug.

Objective:

To evaluate the stability of norepinephrine (64 mg/L) in either normal saline (NS; 0.9% sodium chloride) or 5% dextrose in water (D5W) with storage at either 4°C or room temperature (23°C) in polyvinyl chloride (PVC) bags exposed to or protected from normal room lighting for 2 months.

Methods:

Thirty-two PVC bags were prepared, each containing norepinephrine at 64 mg/L; half of the bags had normal saline as the diluent and the other half had D5W. The bags were stored at either 4°C or room temperature (23°C), with protection from or exposure to ambient fluorescent room light. Overall, there were 4 bags for each combination of diluent, temperature, and light condition. The concentration of norepinephrine in each bag was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 3, 4, 8, 9, 10, 11, 14, 18, 21, 23, 25, 28, 30, 36, 42, and 61.

Results:

Analysis of variance revealed differences in percentage remaining as a function of study day (p < 0.001) and light conditions (p < 0.001), but not diluent (p = 0.06) or storage temperature (p > 0.99).

Conclusions:

Solutions of norepinephrine 64 mg/L in NS or D5W can be stored in PVC bags at 4°C for up to 61 days with protection from light. This expiry date allows for up to 24 h storage at 23°C. Solutions that are not protected from light will retain only 90% of the initial concentration after storage for 39 days at 4°C. This storage period could include up to 24 h at room temperature, without protection from light.     

Stability of Hydromorphone-Ketamine Solutions in Glass Bottles, Plastic Syringes, and IV Bags for Pediatric Use

Objectives:

To evaluate the stability of mixtures of hydromorphone and ketamine in 0.9% sodium chloride (normal saline [NS]) after storage for up to 7 days at room temperature (25°C).

Methods:

The stability of 3 standard mixtures of hydromorphone and ketamine (hydromorphone 0.2 mg/mL + ketamine 0.2 mg/mL, hydromorphone 0.2 mg/mL + ketamine 0.6 mg/mL, and hydromorphone 0.2 mg/mL + ketamine 1.0 mg/mL) in NS was studied. Portions of each mixture were transferred to 3 brown glass bottles (100 mL), 3 plastic syringes (50 mL), and 3 IV bags (50 mL), which were then stored at room temperature (25°C). Physical characteristics, including pH, colour, and precipitation, were evaluated daily. Three 1.5-mL samples were collected from each bottle, syringe, and IV bag at baseline, at 24, 48, and 72 hours, and on day 7. Samples were analyzed in triplicate by a stability-indicating high-performance liquid chromatography method. Solutions were considered stable if they maintained 90% of the initial concentration of each drug. Samples from syringes and IV bags were subjected to standard sterility testing by incubation for 5 days in an enriched culture media.

Results:

No notable changes in pH or colour were observed, and no precipitation occurred in any of the solutions. All formulations maintained more than 90% of the initial concentration of each drug on day 7. No bacterial growth was observed in any of the samples tested.

Conclusions:

Mixtures of hydromorphone and ketamine were stable for up 7 days at 25°C, and the sterility of the preparations was maintained. Because stability alone does not guarantee efficacy, it is recommended that clinical studies be conducted to evaluate the pharmacokinetics and pharmacodynamics of these formulations.     

Stability of Azacitidine in Sterile Water for Injection

Background:

The product monograph for azacitidine states that once reconstituted, the drug may be held for only 30 min at room temperature or 8 h at 4°C. Standard doses result in wastage of a portion of each vial, and the cost of this wastage is significant, adding about $156 000 to annual drug expenditures at the authors’ institution.

Objective:

To evaluate the stability of azacitidine after reconstitution.

Methods:

Vials of azacitidine were reconstituted with sterile water for injection. At the time of reconstitution, the temperature of the diluent was 4°C for samples to be stored at 4°C or −20°C and room temperature for samples to be stored at 23°C. Solutions of azacitidine (10 or 25 mg/mL) were stored in polypropylene syringes and glass vials at room temperature (23°C), 4°C, or −20°C. The concentration of azacitidine was determined by a validated, stability-indicating liquid chromatographic method in serial samples over 9.6 h at room temperature, over 4 days at 4°C, and over 23 days at −20°C. The recommended expiry date was determined on the basis of time to reach 90% of the initial concentration according to the fastest observed degradation rates (i.e., lower limit of 95% confidence interval).

Results:

Azacitidine degradation was very sensitive to temperature but not storage container (glass vial or polypropylene syringe). Reconstitution with cold sterile water reduced degradation. At 23°C, 15% of the initial concentration was lost after 9.6 h; at 4°C, 32% was lost after 4 days; and at −20°C, less than 5% was lost after 23 days.

Conclusions:

More than 90% of the initial azacitidine concentration will be retained, with 97.5% confidence, if, during the life of the product, storage at 23°C does not exceed 2 h, storage at 4°C does not exceed 8 h, and storage at −20°C does not exceed 4 days. These expiry dates could substantially reduce wastage and cost where the time between doses does not exceed 4 days.     

Stability of tiagabine in two oral liquid vehicles.

The stability of tiagabine hydrochloride in two extemporaneously prepared oral suspensions stored at 4 and 25 degrees C for three months was studied. Tiagabine is used for adjunctive therapy for the treatment of refractory partial seizures. It is currently available in a tablet dosage form, which cannot be used in young children who are unable to swallow and given doses in milligrams per kilogram of body weight. No stability data are available for tiagabine in any liquid dosage form. Five bottles contained tiagabine 1 mg/mL in 1% methylcellulose:Simple Syrup, NF (1:6), and another five bottles had tiagabine 1 mg/mL in Ora-Plus:Ora-Sweet (1:1). Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating high-performance liquid chromatographic method (n = 15). At 4 degrees C, the mean concentration of tiagabine exceeded 95% of the original concentration for 91 days in both formulations. At 25 degrees C, the mean concentration of tiagabine exceeded 90% of the original concentration for 70 days in Ora-Plus:Ora-Sweet formulation and for 42 days in 1% methylcellulose:syrup formulation. No changes in pH or physical appearance were seen during this period. The stability data for two formulations would provide flexibility for compounding tiagabine. Tiagabine hydrochloride 1 mg/,mL in extemporaneously prepared liquid dosage forms and stored in plastic bottles remained stable for up to three months at 4 degrees C and six weeks at 25 degrees C.     

Stability of Ertapenem 100 mg/mL in Manufacturer’s Glass Vials or Syringes at 4°C and 23°C

Background:

Prophylactic administration of ertapenem as a single 1-g IV dose has been shown to reduce sepsis after prostate biopsy.

Objective:

To evaluate the stability of ertapenem after reconstitution with 0.9% sodium chloride to a final concentration of 100 mg/mL and storage in the manufacturer’s original glass vials or polypropylene syringes.

Methods:

On study day 0, 100 mg/mL solutions of ertapenem were retained in the manufacturer’s glass vials or packaged in polypropylene syringes and stored at 4°C or 23°C without protection from fluorescent room light. Samples were assayed periodically over 18 days using a validated, stability-indicating liquid chromatographic method with ultra-violet detection. A beyond-use date was determined as the time for the concentration to decline to 90% of the initial (day 0) concentration, based on the fastest degradation rate, with 95% confidence.

Results:

Reconstituted solutions stored in the manufacturer’s glass vials or polypropylene syringes exhibited a first-order degradation rate, such that 10% of the initial concentration was lost in the first 2.5 days when stored at 4°C or within the first 6.75 h when stored at room temperature (23°C). Analysis of variance showed differences in the percentage remaining due to temperature (p < 0.001) and study day (p < 0.001) but not type of container (p = 0.98). When a 95% CI for the degradation rate was calculated and used to determine a beyond-use date, it was established that more than 90% of the initial concentration would remain for 2.35 days at 4°C and for 0.23 day (about 5 h, 30 min) at room temperature.

Conclusions:

A 100 mg/mL ertapenem solution stored in the manufacturer’s glass vial or a polypropylene syringe will retain more than 90.5% of the initial concentration when stored for 48 h at 4°C and for an additional 1 h at 23°C.     

Stability of Diluted Adenosine Solutions in Polyolefin Infusion Bags

Background:

Intravenous or intracoronary adenosine is used in the cardiac catherization lab to achieve maximal coronary blood flow and determine fractional flow reserve.

Objective:

To determine the stability of adenosine 10 and 50 µg/mL in either 0.9% sodium chloride injection or 5% dextrose injection in polyolefin infusion bags stored at 2 temperatures, refrigeration (2°C-8°C) or controlled room temperature (20°C-25°C).

Methods:

Adenosine 10 µg/mL and 50 µg/mL solutions were prepared in 50 mL polyolefin infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection and stored at controlled room temperature or under refrigeration. Each combination of concentration, diluent, and storage was prepared in triplicate. Samples were assayed using stability-indicating, reversed-phase high-performance liquid chromatography immediately at time 0 and at 24 hours, 48 hours, 7 days, and 14 days. Stability was defined as retaining 90% to 110% of the initial adenosine concentration. The samples were also visually inspected against a light background for clarity, color, and the presence of particulate matter.

Results:

After 14 days, all samples retained 99% to 101% of the initial adenosine concentration. No considerable change in pH or visual appearance was noted. The stability data indicated no significant loss of drug due to chemical degradation or physical interactions during storage.

Conclusion:

Adenosine solutions of 10 and 50 µg/mL were stable for at least 14 days in 50 mL polyolefin infusion bags of 0.9% sodium chloride injection or 5% dextrose injection stored at controlled room temperature and refrigerated conditions.