Stability of nizatidine in commonly used intravenous fluids and containers

The stability of nizatidine in commonly used i.v. fluids stored in glass and plastic containers was studied. Stock solutions of nizatidine 0.75, 1.5, and 3.0 mg/mL in 15 i.v. fluids were prepared using nizatidine injection 25 mg/mL. Six 50-mL aliquots of each solution were transferred to separate glass infusion bottles and stored at room temperature or under refrigeration. Twenty-one 40-mL aliquots of additional stock solutions of nizatidine 0.75 and 3.0 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were transferred to polyvinyl chloride (PVC) bags and stored at room or refrigerated temperature; some of these solutions were frozen, thawed, and refrigerated before analysis. Samples of each admixture were analyzed after 0.5, 1, 2, 3, and 7 days of storage for nizatidine concentration using a stability-indicating high-performance liquid chromatographic assay and also for visible changes and pH. The concentration of nizatidine in each admixture remained within 92%-106% of actual initial storage concentration throughout the study period, with the exception of nizatidine 3.0 mg/mL in 8.5% amino acid injection. The stability of nizatidine in admixtures stored in polyvinyl chloride bags was similar to that of admixtures stored in glass bottles. In the i.v. fluids, concentrations, and containers studied, nizatidine admixtures are stable for at least 7 days at either room or refrigerated temperature and 30 days when stored frozen in polyvinyl chloride bags. Admixtures of nizatidine 3.0 mg/mL in 8.5% amino acid injection should not be stored at room temperature for longer than four days.     

Apparent stability of nitroglycerin in dextrose 5% in water.

The apparent stability profile of nitroglycerin (NTG) in dextrose 5% in water when packaged in glass bottles and plastic bags was studied under the following conditions: room temperature (25 +/- 1 C) and room light, room temperature protected from room light, and refrigeration (4 C). NTG stability was assessed by monitoring drug disappearance from solution over a period of five hours after preparation of the admixtures. A spectrophotometric assay was used. There appeared to be no difference in the apparent rate of NTG disappearance when prepared in either glass bottles or plastic bags. Protection of the drug solutions from room light had no apparent effect on the disappearance pattern of NTG. Furthermore, although refrigeration of the NTG solutions appeared to increase the stability of the admixtures, this effect was not seen until approximately four to five hours after preparation of the solutions. It is possible that sorption onto the walls of the glass bottles and plastic bags may account for the observed disappearance of admixed NTG in dextrose 5% in water.     

Amino acid stability and microbial growth in total parenteral nutrient solutions

The stability of amino acids in total parenteral nutrient (TPN) solutions stored for 30 days and the potential for stored TPN solutions to support growth of microbial contaminants were studied. Solutions of 3.5% crystalline amino acids and 25% dextrose with electrolytes were prepared either by using a commercially available amino acid solution with electrolytes or by adding electrolytes individually to a base TPN solution. Solutions were stored in polyvinyl chloride bags at refrigerated (4 degrees C) or room (25 degrees C) temperature for 30 days. Some bags were inoculated with Candida albicans or Pseudomonas maltophilia before storage to serve as positive controls for evaluation of microbial contamination. At appropriate intervals, bags of each type of solution under each storage condition were analyzed for amino acid content. Microbial growth was evaluated by filtering the contents of each bag and incubating the filter in brain-heart infusion broth. No microbial growth was detected in any of the study solutions, but all solutions inoculated with C. albicans and 2 of 16 solutions inoculated with Ps. maltophilia had evidence of growth. No significant decreases in the concentrations of any of the amino acids were noted for solutions stored at refrigerated temperature, but significant decreases in the concentrations of arginine and methionine were noted for solutions stored at room temperature. Total parenteral nutrient solutions can be stored for up to 30 days if they are kept at refrigerated temperatures and protected from light; however, quality assurance measures for these solutions should include end-product microbiologic testing.     

Stability of dobutamine hydrochloride and verapamil hydrochloride in 0.9% sodium chloride and 5% dextrose injections

The stability of dobutamine hydrochloride (250 micrograms/ml) and verapamil hydrochloride (160 micrograms/ml) alone and in combination in 0.9% sodium chloride injection or 5% dextrose injection was studied. Solutions were stored both in plastic i.v. bags and in amber-colored glass bottles at 24 degrees C and 5 degrees C for up to seven days. Before storage and at various times during storage, solutions were assayed at least in triplicate by high-performance liquid chromatography, pH was recorded, and visual appearance was noted. All solutions tested under all conditions retained at least 90% potency for seven days. In plastic i.v. bags, dobutamine either alone or in combination with verapamil in both diluents turned a light-pink color in 24 hours at 24 degrees C. The intensity of the pink color increased with time in 0.9% sodium chloride injection; in 5% dextrose injection, solutions, became clear in 48 hours. The pH of solutions prepared in plastic i.v. bags in 5% dextrose injection decreased from 4.0 to 3.1 during the seven-day period at 24 degrees C; results for solutions in amber bottles were similar. At 5 degrees C, the pH and clarity of all solutions in bags and bottles remained stable for seven days. At the concentrations tested, dobutamine hydrochloride combined with verapamil hydrochloride is stable in 0.9% sodium chloride injection and 5% dextrose injection for 48 hours at 24 degrees C and for seven days at 5 degrees C.     

Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature

The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high-performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen.     

Stability of ganciclovir sodium (DHPG sodium) in 5% dextrose or 0.9% sodium chloride injections

The stability of 9-[(1,3-dihydroxy-2-propoxymethyl]) guanine sodium (ganciclovir sodium, also known as DHPG sodium) in two infusion solutions was studied. Lyophilized ganciclovir sodium 500 mg was reconstituted with sterile water 10 mL to give a theoretical concentration of 50 mg/mL. After reconstitution, 6-mL aliquots of the solution were added to 100 mL of 0.9% sodium chloride injection or 5% dextrose injection in polyvinyl chloride i.v. bags. One sample was withdrawn from each of 10 bags of each solution and analyzed by high-performance liquid chromatography (HPLC). Thirty bags of each solution were then stored under each of the following conditions: at room temperature under laboratory light, at room temperature in the dark, and under refrigeration for up to five days. Single potency assays were performed by HPLC on each of three bags of solution at three and five days after initial dilution of the solutions. The solutions were visually inspected, and the pH of the solutions was measured. All solutions of ganciclovir were stable for at least five days under all storage conditions; mean ganciclovir concentrations did not drop below 98% of initial theoretical values throughout the storage period. No important changes in the pH of the solutions occurred during the study period. Under the conditions of this study, ganciclovir sodium is stable for up to five days when prepared in 5% dextrose injection or 0.9% sodium chloride injection.     

Beyond-use date of extemporaneous morphine hydrochloride oral solution

Hospital pharmacists prepare morphine oral solution extemporaneously in Taiwan because of the unavailability of commercial products. According to the United States Pharmacopeia <795>, extemporaneous oral solution has an expiration of 14 days if there is no stability test data. However, outpatients usually need 4-week medications. The purpose of this study was to determine the beyond-use date of extemporaneous morphine hydrochloride (HCl) oral solution. Extemporaneous 0.1% morphine HCl oral solutions were prepared in an International Organization for Standardization (ISO) Class 8 compounding room, and bottled in 500-mL high-density polyethylene (HDPE) bottles with polypropylene caps. Twelve bottles were divided into 2 groups (sealed or opened daily) and stored under refrigeration or at room temperature to determine the chemical and microbial stabilities. Stability tests of the “sealed” group were performed after 4 weeks, while for the group in which the bottles were shaken and opened twice daily, stability tests were performed weekly. Chemical stability was determined by high performance liquid chromatography and pH, and microbial stability was determined by microbial limit tests according to pharmacopeias. In both groups, all the morphine HCl oral solutions retained more than 90% of the original concentration after 4 weeks, irrespective of whether they were stored at room temperature or in the refrigerator. The pH values were maintained at around 5 during the 4-week study period. All the refrigerated solutions passed the microbial limit tests within 4 weeks, regardless of whether they were sealed or opened twice daily. All the solutions stored at room temperature retained their microbial stability in the 1st week. However, mold and yeast counts exceeded the limits during the 2nd week in the “opened daily” group. Extemporaneous 0.1% morphine HCl oral solutions prepared in an ISO Class 8 clean room have a beyond-use date of 4 weeks in HDPE bottles when refrigerated. The beyond-use date decreased to 1 week when stored at room temperature. Extrapolation of this result may be limited by different compounding environments, containers or formulations.     

Stability of vancomycin hydrochloride in 5% dextrose and 0.9% sodium chloride injections

The stability of vancomycin hydrochloride mixed with 5% dextrose and 0.9% sodium chloride injections was studied. Vancomycin hydrochloride powder was mixed with each of the two diluents in final concentrations of 5 mg/mL. Duplicate samples of each admixture were divided into four parts and stored at 24 degrees C in glass and in plastic i.v. bags for 17 days and at 5 degrees C and -10 degrees C in glass for 63 days. To additional samples, hydrochloric acid or phosphate buffer was added; these were stored at 24 degrees C for 17 days. At various storage times, clarity and pH of the samples were recorded and vancomycin concentrations were measured in triplicate by high-performance liquid chromatography. Except for the buffered samples, all solutions remained clear and pH was unchanged. Vancomycin concentrations decreased less than 6% during 17 days at room temperature. In the refrigerated and frozen samples, vancomycin concentrations decreased less than 1% throughout the study. Vancomycin hydrochloride is stable in admixtures with 5% dextrose injection and 0.9% sodium chloride injection for 17 days at 24 degrees C and for 63 days at 5 degrees C and -10 degrees C.     

Effect of freezing and microwave thawing on the stability of six antibiotic admixtures in plastic bags

The stability of six antibiotics in intravenous fluids in polyvinyl chloride containers after freezing and microwave-thawing is reported. Tobramycin sulfate 160 mg, amikacin sulfate 1 g, ticarcillin disodium 3 g, clindamycin phosphate 300 mg, nafcillin sodium 1 g, and ampicillin sodium was also diluted in plastic bags of 0.9% sodium chloride injection 50 ml. For each antibiotic except ampicillin sodium, three bags were prepared and assayed immediately for antibiotic content. Two of the bags were frozen at -20 degrees C for 30 days and then thawed, one by exposure to room-temperature air and the other by microwave radiation. Each was assayed immediately and after 8 and 24 hours storage at room temperature. The third bag was not frozen, but was stored at room temperature and assayed at 8 and 24 hours. Five bags of ampicillin sodium were prepared-three in 0.9% sodium chloride, which were frozen at -20, -30, and -70 degrees C, and two in 5% dextrose, which were frozen at -30 and -70 degrees C. All ampicillin solutions were stored 30 days, assayed, microwave-thawed, and assayed again. All antibiotics except ampicillin retained 90% or more potency when microwave-thawed after storage at -20 degrees C for 30 days, and after subsequent storage at room temperature for 24 hours. Ampicillin sodium was stable in 0.9% sodium chloride when stored at -30 or -70 degrees C, microwave-thawed, and stored up to eight hours at room temperature. Ampicillin sodium was stable in 5% dextrose when stored at -70 degrees C and microwaved-thawed, but its potency declined to 70.5% after eight hours storage at room temperature.     

Stability of intravenous nitroglycerin solutions

The stability of intravenous nitroglycerin solutions prepared from either sublingual tablets or a 10% nitroglycerin-lactose adsorbate (powder) was examined under various conditions. Nitroglycerin concentration was measured by high-pressure liquid chromatography. Nitroglycerin stock solutions (0.8-1.0 mg/ml) prepared from tablets or powder in either 0.9% saline were stored upright in refrigerated multidose vials for 6 months without a significant decrease in concentration. Storage of the solutions at room temperature resulted in a 20% loss after 3 months. Intravenous nitroglycerin solutions (0.2 mg/ml) prepared from tablets or powder in 0.9% saline or 5% dextrose in water were stored in glass intravenous bottles at temperatures between 6 and 38 degrees for 24 hr with a maximum loss of 18%. Stability was not affected by light. Solutions in contact with rubber stoppers, plastic intravenous bags, or plastic administration sets exhibited decreased nitroglycerin concentration characteristic of sorption. Nitroglycerin concentrations decreased to a greater extent when the administration sets were equipped with plastic burets. Brief contact of nitroglycerin solutions with a plastic syringe did not result in decreased concentration. The stability of intravenous nitroglycerin solutions packaged in glass was not dependent on light, the vehicle, or the source of nitroglycerin. Contact with rubber or plastic surfaces should be minimized.     

Stability of ampicillin trihydrate suspension in amber plastic oral syringes

The stability of ampicillin trihydrate oral suspension stored in amber plastic oral syringes was studied. Commercially available ampicillin trihydrate powder for oral suspension was reconstituted according to manufacturer's instructions and drawn into 5-mL amber polypropylene plastic oral syringes. The syringes were divided into groups and stored at -20, 4, 25, 60, or 80 degrees C. Powder from two additional lots was similarly reconstituted and packaged and stored at 80 degrees C only to assess interlot variability. Immediately after reconstitution and at specified times during storage, three syringes at each storage temperature were removed and their contents analyzed for ampicillin trihydrate concentration by a spectrophotometric assay. Samples stored at frozen (-20 degrees C) or refrigerated (4 degrees C) temperature retained at least 90% of the initial ampicillin concentration throughout the 47-day study period. Samples stored at room temperature retained at least 90% of the initial ampicillin concentration for 30 days and exhibited an apparent zero-order degradation rate. Samples stored at heated temperatures (60 and 80 degrees C) exhibited an apparent first-order degradation process, with the concentration of ampicillin decreasing to less than 90% of initial concentration within two hours. Reconstituted ampicillin trihydrate powder for oral suspension is stable for at least 30 days when stored at room, refrigerated, or frozen temperature in the amber plastic oral syringes studied. The expiration dates recommended by the manufacturer for ampicillin trihydrate suspension stored in its original container can also be used for reconstituted suspension stored in these amber plastic syringes.     

Nifedipine stability in cardioplegic solution

The stability of nifedipine in cardioplegic solution was studied. Cardioplegic solutions containing nifedipine at 275 and 500 micrograms/liter were stored in plastic bags covered in brown plastic wrappers (1) under normal room light at 25 degrees C and (2) in a dark refrigerator at 4 degrees C. Samples were removed periodically for 48 hours. Infusions of cardioplegic solution containing 275 micrograms/liter were simulated using tubing and flow rates of 100, 200, and 300 ml/min; bags were covered with aluminum foil, while tubing was exposed to normal room lighting or yellow lighting, which does not degrade nifedipine. Gas chromatography was used for nifedipine assays. Nifedipine degraded more rapidly at 25 degrees C than at 4 degrees C. However, even when protected from light and refrigerated, nifedipine concentrations declined to less than 90% of original potency by approximately six hours after preparation. There was no significant degradation during the simulated infusion regardless of light exposure or flow rate. Cardioplegic solutions containing nifedipine should be prepared immediately before the surgical procedure, refrigerated until use, and protected from light until administration.     

Stability of miconazole in peritoneal dialysis fluid

The stability of miconazole when mixed with peritoneal dialysis (PD) fluid and stored in plastic bags or glass ampuls was determined. Admixtures of miconazole and PD fluid were prepared in 2-L polyvinyl chloride (PVC) bags and in 1-mL glass ampuls to give a nominal initial concentration of 20 mg/mL. Duplicate samples of each solution were assayed in duplicate by high-performance liquid chromatography immediately after preparation and at various intervals up to nine days. All admixtures were stored in ambient light at 20 +/- 2 degrees C. A substantial loss of miconazole (greater than 10% of the initial concentration) occurred within four hours for admixtures stored in PVC bags, whereas similar solutions retained more than 90% of their initial miconazole concentration for at least three days when stored in glass ampuls under the same conditions. This suggests that the observed loss of miconazole from the PVC bags was largely due to an interaction with the container, rather than to chemical degradation in solution. About 28% of the miconazole lost from the solution during storage in PVC bags was recovered from the plastic by methanolic extraction. The rapid loss of miconazole when the drug was mixed with PD fluid and stored in PVC bags indicates that such admixtures should be prepared immediately before administration.     

Stability and sorption of FK 506 in 5% dextrose injection and 0.9% sodium chloride injection in glass, polyvinyl chloride, and polyolefin containers.

The effects of the diluent, the storage container, light, and infusion through various types of tubing on the stability and sorption of FK 506 were studied. Solutions of FK 506 in 0.9% sodium chloride injection or 5% dextrose injection were stored at room temperature (24 +/- 2 degrees C) in glass i.v. bottles, polyvinyl chloride (PVC) minibags, and polyolefin containers. FK 506 solution in 0.9% sodium chloride injection was stored in plastic syringes at room temperature and either exposed to normal room light or stored in the dark. FK 506 solution in 5% dextrose injection was placed in plastic syringes and infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, and fat emulsion tubing over a two-hour period. The infused samples and samples collected from the containers and syringes at intervals up to 48 hours were analyzed for FK 506 concentration by high-performance liquid chromatography. FK 506 concentrations remained greater than 90% of initial concentration for admixtures in 5% dextrose injection stored in glass bottles for 48 hours and for admixtures in 5% dextrose injection or 0.9% sodium chloride injection stored in polyolefin containers for 48 hours. No change in concentration was measured for admixtures in 0.9% sodium chloride injection stored in plastic syringes, and exposure to light did not affect the stability of FK 506 solution. No substantial change in concentration occurred in FK 506 solution in 5% dextrose injection infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, or fat emulsion tubing. FK 506 admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection should be stored in polyolefin containers. If polyolefin containers are not available, solutions should be prepared with 5% dextrose injection and stored in glass bottles.     

Stability of fentanyl citrate and bupivacaine hydrochloride in portable pump reservoirs

The stability of fentanyl citrate and bupivacaine hydrochloride in an admixture with 0.9% sodium chloride injection in portable pump reservoirs with or without overwraps was investigated. Twelve 100-mL samples containing fentanyl 20 micrograms/mL and bupivacaine hydrochloride 1250 micrograms/mL were placed in the plastic drug reservoirs, and 1-mL quantities were withdrawn immediately after preparation and at intervals during 30 days of storage. Six reservoirs were refrigerated (3 degrees C) and six stored at room temperature (23 degrees C); three at each temperature were placed in overwraps. All samples were observed for precipitation and for change in color or pH and were analyzed for drug concentration by high-performance liquid chromatography. No precipitation or change in color or pH was observed during the 30-day storage period. No loss of fentanyl or bupivacaine was detected in either the wrapped or the unwrapped samples. Fentanyl citrate and bupivacaine hydrochloride in 0.9% sodium chloride injection appear to be compatible, and admixtures containing the two drugs at the concentrations studied can be stored without overwraps for up to 30 days at refrigerated or room temperature without any significant loss of potency.     

Stability of allopurinol and of five antineoplastics in suspension

The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.     

Stability of dacarbazine in amber glass vials and polyvinyl chloride bags.

The stability of dacarbazine in commercial glass vials and polyvinyl chloride (PVC) bags in various storage conditions and the emergence of 2-azahypoxanthine, a major degradation product possibly linked with some adverse effects, were studied. Triplicate samples of reconstituted (11 mg/mL) and diluted (1.40 mg/mL) dacarbazine admixtures were prepared and stored at 4 degrees C or at 25 degrees C in daylight, fluorescent light, or the dark. The effect of several light-protective measures (amber glass vials, aluminum foil wrapping, and opaque tubing) on dacarbazine stability in a simulated i.v. infusion system was also evaluated. Dacarbazine quantification and main degradation product determination were performed by high-performance liquid chromatography. Stability was defined as conservation of 90-105% of initial dacarbazine concentration without major variations in clarity, color, or pH and without precipitate formation. Reconstituted dacarbazine solutions were stable for 24 hours at room temperature and during light exposure and stable for at least 96 hours at 2-6 degrees C when stored in the dark. After dilution in PVC bags, stability time increased from 2 hours in daylight to 24 hours in fluorescent light and to 72 hours when covered with aluminum foil. After two hours of simulated infusion, dacarbazine remained stable. Diluted dacarbazine solutions stored at 2-6 degrees C were stable for at least 168 hours. The only degradation product found was 2-azahypoxanthine, which was detected in every sample. The storage and handling of dacarbazine should take into account both the loss of the drug and the production of its potentially toxic degradation product. Dacarbazine must be carefully protected from light, administered using opaque infusion tubing, and, if necessary, refrigerated before administration to reduce 2-azahypoxanthine formation.     

Stability of penicillin V potassium in unit dose oral syringes.

The stability of reconstituted penicillin V potassium (PVK) when stored in 6-ml plastic oral syringes at various temperatures and protected from light was studied. One batch of PVK was reconstituted with distilled water according to manufacturer's directions (label claim: 125 mg/ml). Samples of 5 ml were stored in plastic oral syringes at 4 C, 25 C, 41 C, 60 C or 75 C and assayed spectrophotometrically and microbiogically at various times. From an initial concentration of 113% of label claim, PVK stored at 4 C (refrigerated) reached 90% of manufacturer's label claim in 11.5 days (95% confidence level). PVK stored at 25 C (room temperature) was unstable after storage for less than 37 hours. PVK degradation followed a first-order process. No significant difference was found between the spectrophotometric and microbiological assay (p less than 0.05). Manufacturer's stability data for storage of reconstituted PVK in the original bulk container should not be applied to PVK repackaged in plastic oral syringes. The pharmacy department developed guideliness designed to prevent the administration of subpotent PVK.     

Physical and chemical stability of gemcitabine hydrochloride solutions.

OBJECTIVE: To evaluate the physical and chemical stability of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) solutions in a variety of solution concentrations, packaging, and storage conditions. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test conditions included (1) reconstituted gemcitabine at a concentration of 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride or sterile water for injection in the original 200 mg and 1 gram vials; (2) reconstituted gemcitabine 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride injection packaged in plastic syringes; (3) diluted gemcitabine at concentrations of 0.1 and 10 mg/mL as the hydrochloride salt in polyvinyl chloride (PVC) minibags of 0.9% sodium chloride injection and 5% dextrose injection; and (4) gemcitabine 0.1, 10, and 38 mg/mL as the hydrochloride salt in 5% dextrose in water and 0.9% sodium chloride injection as simulated ambulatory infusions at 32 degrees C. Test samples of gemcitabine hydrochloride were prepared in the concentrations, solutions, and packaging required. MAIN OUTCOME MEASURES: Physical and chemical stability based on drug concentrations initially and after 1, 3, and 7 days of storage at 32 degrees C and after 1, 7, 14, 21, and 35 days of storage at 4 degrees C and 23 degrees C. RESULTS: The reconstituted solutions at a gemcitabine concentration of 38 mg/mL as the hydrochloride salt in the original vials occasionally exhibited large crystal formation when stored at 4 degrees C for 14 days or more. These crystals did not redissolve upon warming to room temperature. All other samples were physically stable throughout the study. Little or no change in particulate burden or the presence of haze were found. Gemcitabine as the hydrochloride salt in the solutions tested was found to be chemically stable at all concentrations and temperatures tested that did not exhibit crystallization. Little or no loss of gemcitabine occurred in any of the samples throughout the entire study period. However, refrigerated vials that developed crystals also exhibited losses of 20% to 35% in gemcitabine content. Exposure to or protection from light did not alter the stability of gemcitabine as the hydrochloride salt in the solutions tested. CONCLUSION: Reconstituted gemcitabine as the hydrochloride salt in the original vials is chemically stable at room temperature for 35 days but may develop crystals when stored at 4 degrees C. The crystals do not redissolve upon warming. Gemcitabine prepared as intravenous admixtures of 0.1 and 10 mg/mL as the hydrochloride salt in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as a solution of 38 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes is physically and chemically stable for at least 35 days at 4 degrees C and 23 degrees C. Gemcitabine as the hydrochloride salt is stable for at least 7 days at concentrations of 0.1, 10, and 38 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection stored at 32 degrees C during simulated ambulatory infusion.     

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.