Accuracy of delivery of cefazolin, chloramphenicol, and vancomycin by a controlled-release membrane infusion device

The effects of flow rate and drug concentration on the accuracy of in vitro delivery of cefazolin, chloramphenicol, and vancomycin by a new controlled-release membrane infusion device, MICROS, were studied. Cefazolin, chloramphenicol, and vancomycin 1 g in sterile water for injection 10 mL were injected into the drug chamber of the device and delivered through an administration set with 0.9% sodium chloride injection from a primary line. Drug delivery was studied at four flow rates (0.5, 1.0, 1.5, and 2.0 mL/min). In addition, three concentrations of each drug (25, 50, and 100 mg/mL for cefazolin and vancomycin, and 50, 100, and 200 mg/mL for chloramphenicol) were studied at a fixed flow rate of 1 mL/min. Samples were collected in triplicate every 2.5-5.0 minutes using a fraction collector over a 90-minute period for cefazolin and a 120-minute period for chloramphenicol and vancomycin. The concentration of each drug was measured by high-performance liquid chromatography. At various flow rates, the time for delivery of greater than or equal to 95% of each dose ranged from 30 to 55 minutes for cefazolin, 45 to 70 minutes for chloramphenicol, and 50 to 65 minutes for vancomycin. At various concentrations, greater than or equal to 95% of each dose was delivered in 40 to 55 minutes for cefazolin, 40 to 70 minutes for chloramphenicol, and 50 to 60 minutes for vancomycin. The desired delivery times were 30-60 minutes for cefazolin and chloramphenicol and 50-70 minutes for vancomycin. Delivery of cefazolin and vancomycin by the MICROS membrane infusion system was accurate. Some delay was encountered in the delivery of chloramphenicol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temperature of refrigerated i.v. fluids and admixtures during infusion

The effects of infusion rate, drop size, and solution composition on the infusion temperature of i.v. fluids and admixtures that had been stored at refrigerated temperatures were determined. Polyvinyl chloride bags containing 5% dextrose injection, 0.9% sodium chloride injection, cefazolin 20 mg/mL in 5% dextrose injection, or total parenteral nutrient (TPN) solution were removed from the refrigerator after 12 hours and hung from i.v. poles. An administration set was attached to each bag, and the distal end of the administration tubing was placed in a beaker-funnel-flask apparatus that served as a collection vessel for effluent during simulated i.v. infusions. Thermo-couples were inserted into each i.v. bag and positioned under the distal end of each administration set to monitor the temperatures of the solution in the bag and of the effluent. 5% Dextrose injection and 0.9% sodium chloride injection were studied at two flow rates (125 and 60 mL/hr) using two different administration sets (60-drops/mL microdrip set and 15-drops/mL primary set); the cefazolin admixture and the TPN solution were studied at both flow rates using the primary set only. The temperatures at each probe were measured in triplicate at the start of each infusion and at 3, 6, 9, 12, 15, and 25 minutes during the infusion; each infusion was repeated three times. All of the solutions warmed significantly as they passed through the administration sets. Throughout all time intervals, the cefazolin admixtures had the smallest proximal-distal temperature increase, and the TPN solutions had the greatest increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of ranitidine hydrochloride at dilute concentration in intravenous infusion fluids at room temperature

The stability of ranitidine at low concentration (0.05 mg/mL) in five intravenous infusion solutions (0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose with 0.45% sodium chloride, and 5% dextrose with lactated Ringer's injections) was studied. Admixtures were stored for seven days at room temperature in 150-mL and 1-L polyvinyl chloride infusion bags. Ranitidine stability in 0.9% sodium chloride injection and in 5% dextrose injection was also examined for up to 28 days, and these data were compared with data obtained at higher ranitidine concentrations (0.5-2.0 mg/mL). At intervals during the storage periods, color, clarity, and solution pH were examined and ranitidine content was determined by a stability-indicating high-performance liquid chromatographic assay. Ranitidine content remained greater than 90% of the initial concentration for more than 48 hours in all infusion fluids except 5% dextrose with lactated Ringer's injection. No visual changes or appreciable changes in pH were observed for any of the solutions. At the dilute concentration, ranitidine was markedly more stable after eight hours in 0.9% sodium chloride injection than in 5% dextrose injection. In 0.9% sodium chloride injection, ranitidine concentrations remained above 95% for up to 28 days, but drug concentrations in 5% dextrose injection fell below 90% after seven days. Stability in 5% dextrose injection improved as ranitidine concentrations increased from 0.05 to 2.0 mg/mL. Ranitidine (0.05 mg/mL) is stable for at least 48 hours at room temperature in all infusion fluids tested except 5% dextrose with lactated Ringer's injection.     

Stability of amrinone and digoxin, procainamide hydrochloride, propranolol hydrochloride, sodium bicarbonate, potassium chloride, or verapamil hydrochloride in intravenous admixtures.

The stability of amrinone and digoxin, procainamide hydrochloride, propranolol hydrochloride, sodium bicarbonate, potassium chloride, or verapamil hydrochloride in intravenous admixtures was studied. Admixtures of amrinone and digoxin were studied at one concentration. Amrinone admixtures with propranolol hydrochloride, sodium bicarbonate, potassium chloride, and verapamil hydrochloride were studied at two concentrations. In general, 0.45% sodium chloride injection was used as the diluent; 5% dextrose injection was also used for the procainamide hydrochloride experiments. Duplicate solutions of each test admixture and single-drug control admixture were prepared and stored for four hours at 22-23 degrees C under fluorescent light. Samples were analyzed by visual inspection, tested for pH, and assayed by high-performance liquid chromatography. Admixtures containing amrinone 1.25 or 2.5 mg/mL (as the lactate salt) and sodium bicarbonate 37.5 mg/mL precipitated immediately or within 10 minutes. No changes in pH or visual appearance were noted for amrinone admixtures with procainamide hydrochloride, digoxin, propranolol hydrochloride, potassium chloride, and verapamil hydrochloride. Appreciable degradation of both amrinone and procainamide was observed after four hours when the two were mixed in 5% dextrose. No degradation of amrinone or procainamide was seen when the 5% dextrose was replaced by 0.45% sodium chloride. Amrinone and sodium bicarbonate were incompatible in intravenous admixtures. Amrinone was compatible with digoxin, propranolol hydrochloride, potassium chloride, and verapamil hydrochloride. Amrinone and procainamide were compatible in 0.45% sodium chloride injection but not in 5% dextrose injection.     

Osmolality of small-volume i.v. admixtures for pediatric patients

The osmolalities of pediatric i.v. admixtures were measured to identify drug concentrations in selected vehicles that would conserve fluid while maintaining osmolality values of 400 mOsm/kg or less. Test solutions were prepared by diluting appropriate volumes of freshly reconstituted powdered drug products or commercially diluted drug products with 5% dextrose injection, 0.9% sodium chloride injection, or both to provide 5 mL of each admixture at desired drug concentrations. To reduce their osmolalities, trimethoprim-sulfamethoxazole and ampicillin sodium were also diluted in 0.45% sodium chloride injection; ticarcillin disodium was diluted only in 0.45% sodium chloride injection. A vapor pressure osmometer was used to measure osmolalities in triplicate for three solutions prepared for each admixture. Of the 63 different admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection or both, 47 (75%) had osmolalities of 400 mOsm/kg or less. At least one concentration of each selected drug diluted in these vehicles had an osmolality of less than 425 mOsm/kg, except for trimethoprim-sulfamethoxazole and ampicillin sodium. Selected concentrations of the latter two drugs and ticarcillin disodium in 0.45% sodium chloride injection resulted in acceptable osmolalities. For most drugs diluted to the same concentration in 5% dextrose injection and 0.9% sodium chloride injection, osmolalities were lower in the dextrose solutions. Selection of an appropriate vehicle and drug concentration can control the osmolality of i.v. admixtures when the volume of fluid must be minimized, as for pediatric patients.     

Administrating incompatible drugs by a retrograde intravenous infusion system

Use of a retrograde infusion system for concurrent intravenous administration of two incompatible drugs separated by a barrier fluid was studied. Four different barrier fluids (5% dextrose injection, 10% dextrose injection, 0.9% sodium chloride injection, and sterile water for injection) were used to separate sodium bicarbonate and calcium chloride. The primary infusion was 5% dextrose injection. The delivery system was visually inspected for formation of precipitate (calcium carbonate) upon addition of the two drug solutions and 2 ml of the barrier fluid. If precipitation occurred, the procedure was repeated, increasing the volume of barrier fluid incrementally until no precipitate could be seen. If no precipitate was seen with the initial 2 ml of barrier fluid, the volume of barrier fluid was decreased until precipitation occurred. These procedures were repeated for each barrier fluid at flow rates of 5-20 ml/hr for 90 minutes. The minimum volume of barrier fluid needed to prevent precipitate formation was determined in triplicate at each flow rate. The minimum volume of barrier fluid that prevented precipitate formation was approximately 2.0 ml. This volume did not differ significantly by barrier solution type or by flow rate. Sodium bicarbonate and calcium chloride can be administered concurrently by the retrograde intravenous method without visual incompatibility when separated by greater than or equal to 2 ml of barrier fluid, and this method can probably be used for administration of other potentially incompatible drugs.     

Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions

The stability of cisplatin, iproplatin, carboplatin, and tetraplatin in common intravenous solutions was studied. Admixtures of each drug in each of the following vehicles were prepared in glass containers: 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection (admixtures were prepared in plastic bags also), and 5% dextrose and 0.225% sodium chloride injection. Drug concentrations were monitored for 24 hours using stability-indicating high-performance liquid chromatographic methods. The stability of cisplatin and tetraplatin was related to the chloride ion content of the infusion fluid; when the infusion fluid contained 0.9% sodium chloride, each of these drugs was present at greater than 90% of the original concentration after six hours. The stability of iproplatin was not related to chloride concentration. A slight increase in the decomposition rate of carboplatin was observed in the presence of chloride ion. Carboplatin and iproplatin are stable for 24 hours in all the infusion fluids studied, but carboplatin should not be diluted with solutions containing chloride ions because of possible conversion to cisplatin. Cisplatin is stable for 24 hours in admixtures containing sodium chloride concentrations of 0.3% or greater. Tetraplatin is stable for six hours in admixtures containing sodium chloride concentrations of at least 0.018%.     

Effect of vehicle ionic strength on sorption of nitroglycerin to a polyvinyl chloride administration set

The nitroglycerin sorptive properties of a polyvinyl chloride i.v. administration set were studied, and the role played by the admixture vehicle in this process was explored. Admixtures of nitroglycerin 0.4 mg/mL were prepared in sterile water for injection, 5% dextrose injection, Ringer's injection, and 0.25%, 0.9%, and 5% sodium chloride injection. Each admixture was divided into two 500-mL sterile glass containers, and flow through the administration set at 100 mL/hr was begun. Samples of effluent were collected at intervals beginning 10 minutes after the start of the infusion and ending at 180 minutes. Nitroglycerin depletion from solution and uptake by the set was determined by an ultraviolet spectrophotometric assay. Initially, the degree of nitroglycerin loss to the set was greatest for dextrose admixtures, intermediate for water admixtures, and least for sodium chloride admixtures. Losses of about 40% were observed during the first 10 minutes; between 15 and 20 minutes, the stated pattern of drug sorption was reversed, with sodium chloride admixtures now showing the greatest loss of nitroglycerin. The availability of nitroglycerin was an inverse function of increasing ionic strength during the three-hour observation period. Nitroglycerin availability in admixtures in contact with a polyvinyl chloride administration set was dependent on the ionic strength of the vehicle and the time points in the infusion period at which measurements were made.     

Stability of an ofloxacin injection in various infusion fluids.

The stability of ofloxacin was evaluated in 10 different infusion fluids under various storage conditions. Solutions of ofloxacin (0.4 mg/mL and 4.0 mg/mL) were prepared in (1) 0.9% sodium chloride injection; (2) 5% dextrose injection; (3) 5% dextrose and 0.9% sodium chloride injection; (4) 5% dextrose and lactated Ringer's injection; (5) 5% sodium bicarbonate injection; (6) Plasma-Lyte 56 and 5% dextrose injection; (7) 5% dextrose, 0.45% sodium chloride, and 0.15% potassium chloride injection; (8) 1/6 M sodium lactate injection; (9) water for injection; and (10) 20% mannitol injection. Each solution was injected into polyvinyl chloride bags and stored at (1) 24 degrees C for 3 days, (2) 5 degrees C for 7 days, (3) 5 degrees C for 14 days, (4) -20 degrees C for 13 weeks and then 5 degrees C for 14 days, or (5) -20 degrees C for 26 weeks and then 5 degrees C, for 14 days. Samples were assayed initially and after storage by high-performance liquid chromatography and examined for visual clarity, pH, turbidity, and particulates. Ofloxacin was stable in all solutions and under all storage conditions. All of the solutions were clear, pH was stable, and particulate-matter counts were acceptable under all storage conditions (except for the 20% mannitol solution, which formed crystals at 5 degrees C and -20 degrees C). An injectable formulation of ofloxacin was stable for at least 3 days at 24 degrees C, 14 days at 5 degrees C, and 26 weeks at -20 degrees C in all tested infusion fluids. Crystals formed in refrigerated or frozen solutions prepared with 20% mannitol injection.     

Delivery of gentamicin by a controlled-release infusion system versus a minibag system

Delivery of gentamicin via a new controlled-release intravenous infusion system was compared with conventional delivery via small-volume injections in minibags by measuring serum drug concentrations in 10 healthy men. Each volunteer received gentamicin (as the sulfate salt) 2 mg/kg. In phase 1, subjects randomly received the drug either as a 50-mL admixture in 5% dextrose injection (D5W) or from the controlled-release system (CRIS, IVAC Corporation), in which drug was diluted in a vial with 10 mL of sterile water for injection (density of drug solution, approximately 1.5% w/v) and was delivered when the primary solution (D5W; density, 5% w/v) displaced drug from the vial and infused it into the subject over 30 min; subjects were then crossed over. In phase 2, nine of the subjects received the drug via CRIS with the diluent changed to 10 mL of 5% dextrose and 0.9% sodium chloride injection (D5NS; density of drug solution, approximately 5.9% w/v). In phase 3, 10 men (seven of the original subjects) received the gentamicin dose via CRIS with 20 mL of D5NS as the diluent or via minibags in a crossover design. The amount of drug remaining in each vial used with the CRIS system was determined. Drug administration via CRIS with 10 mL of sterile water diluent resulted in serum concentrations approximately 35% of those obtained with the minibag system, and a substantial portion (71 +/- 8%) of the dose to be administered remained in the vials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activity of urokinase diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored in glass or plastic syringes

The effects of the diluent, the container, the i.v. set, and the drug concentration on the adsorption of urokinase to i.v. administration systems were studied, along with the compatibility of urokinase with plastic and glass syringes. Solutions of urokinase 1500 and 5000 IU/mL in 0.9% sodium chloride injection and 5% dextrose injection in glass and polyvinyl chloride (PVC) containers were sampled at 2 and 30 minutes. Administration sets were attached to PVC containers containing the urokinase-5% dextrose injection solutions, and samples were collected at 90 and 150 minutes. Glass and polypropylene syringes containing urokinase 5000 IU/mL in 0.9% sodium chloride injection or 5% dextrose injection were sampled at 0, 4, 8, and 24 hours. Urokinase activity was measured by an in vitro clot lysis assay. No urokinase diluted in 0.9% sodium chloride injection adsorbed to glass or PVC containers. For urokinase 1500 IU/mL in 5% dextrose injection, a loss of 15% to 20% occurred almost instantaneously in PVC containers; additional losses to the infusion sets were minimal. However, for urokinase 5000 IU/mL in 5% dextrose injection, no losses were observed in the PVC systems. No drug loss to glass bottles was seen for urokinase 1500 or 5000 IU/mL in 5% dextrose injection. Urokinase potency remained constant in polypropylene and glass syringes for 24 hours. To minimize urokinase sorption to PVC containers, higher concentrations of urokinase diluted in 5% dextrose injection should be used, provided that clinical safety and efficacy are not compromised. The use of 0.9% sodium chloride injection as a diluent also prevents sorption losses.     

Stability of intravenous admixtures containing aztreonam and cefazolin

The stability of aztreonam and cefazolin in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride containers: aztreonam 20 mg/mL and cefazolin 20 mg/mL (as the sodium salt); aztreonam 10 mg/mL and cefazolin 5 mg/mL; aztreonam 20 mg/mL and cefazolin 5 mg/mL; and aztreonam 10 mg/mL and cefazolin 20 mg/mL. One of each of these admixtures was stored at 23-25 degrees C for 48 hours and at 4-5 degrees C for seven days. At various storage times the admixtures were inspected for visual changes, and 1-mL samples were tested for pH and assayed using a stability-indicating high-performance liquid chromatographic assay. No visual changes were observed, and changes in pH were negligible. Concentrations of aztreonam and cefazolin under both storage conditions decreased by less than 3%. Intravenous admixtures of aztreonam and cefazolin at the concentrations studied are stable for at least 48 hours at 23-25 degrees C and for seven days at 4-5 degrees C.     

Stability and compatibility of fluorouracil and mannitol during simulated Y-site administration.

The stability and compatibility of fluorouracil admixtures with mannitol during simulated Y-site administration was studied. Fluorouracil injection 50 mg/mL was diluted with 5% dextrose injection, 0.9% sodium chloride injection, and 5% dextrose and 0.45% sodium chloride injection to final concentrations of 1 and 2 mg/mL. Combinations of fluorouracil admixtures with 20% mannitol injection were made using equal volumes in glass test tubes; immediately after mixing and at one, two, and four hours, the samples were examined for visual incompatibilities. Duplicate combinations of fluorouracil admixtures with 20% mannitol injection were made using equal volumes in plastic syringes; immediately after mixing with internal standard in glass test tubes and at 2, 4, 8, and 24 hours, samples were removed for chemical analysis. A high-performance liquid chromatographic assay was used to determine fluorouracil concentrations. No evidence of precipitation, color change, or haze was observed. During the 24-hour study, fluorouracil concentrations remained within 6% of initial concentrations for all combinations with mannitol. Fluorouracil 1 and 2 mg/mL in 5% dextrose injection, 0.9% sodium chloride injection, and 5% dextrose and 0.45% sodium chloride injection was chemically stable and visually compatible when combined with 20% mannitol injection during simulated Y-site administration.     

Stability and preservative effectiveness of treprostinil sodium after dilution in common intravenous diluents.

The stability of treprostinil sodium after dilution in three common i.v. infusion vehicles was assessed. The chemical stability of treprostinil sodium was tested over a 48-hour period at 40 degrees C and 75% relative humidity after dilution in each of three diluents: sterile water for injection, 0.9% sodium chloride injection, and 5% dextrose injection, and after passage through an i.v. delivery system. Chemical analysis was conducted by using a validated stability-indicating high-performance liquid chromatographic assay, visually inspecting the solutions, and measuring the pH of each solution. The preservative effectiveness of the solutions was tested by the recovery of inoculations of compendial microorganisms after 48 hours in dilute solutions of treprostinil sodium. All assay results for treprostinil were within 90.0% to 110.0% of the prepared solutions diluted at 0.004 and 0.13 mg/mL treprostinil sodium in sterile water for injection and 0.9% sodium chloride injection. The assay results were the same for dilute treprostinil solutions in 5% dextrose injection at concentrations of 0.02 and 0.13 mg/mL. The pH values for these solutions remained within acceptable values of 6.0 to 7.2 for the stability study. No change in physical appearance or any visible particulate matter was observed. Approximately 70% of metacresol, the preservative, in the dilute treprostinil sodium solutions was removed before reaching the terminal end of the tubing. None of the dilute treprostinil sodium solutions supported microbial growth in the cassette reservoirs for the organisms considered. Treprostinil sodium 0.13 mg/mL solution in sterile water for injection, 0.9% sodium chloride for injection, and 5% dextrose for injection appeared to be stable after storage in controlled ambulatory drug-delivery systems for 48 hours at 40 degrees C and 75% relative humidity. Treprostinil sodium 0.004 mg/mL in sterile water and 0.9% sodium chloride for injection and 0.02 mg/mL in 5% dextrose injection was also stable under the same conditions. None of the solutions showed signs of microbial growth.     

Stability of milrinone lactate in the presence of 29 critical care drugs and 4 i.v. solutions.

The stability of milrinone lactate in the presence of 29 critical care drugs during simulated Y-site injection and in 4 i.v. solutions was studied. Ten milliliters of milrinone 400 microg/mL (as the lactate salt) was combined with 10 mL of each of 29 commonly used critical care drugs in 5% dextrose injection. Also, mixtures containing milrinone 400 microg/ mL in lactated Ringer's injection, 5% dextrose injection, 0.45% sodium chloride injection, and 0.9% sodium chloride injection were prepared. All mixtures were prepared in triplicate and stored at 22-23 degrees C in glass containers or polyvinyl chloride bags under fluorescent light. Samples were withdrawn zero, one, two, and four hours after mixing for each milrinone-secondary drug mixture and at intervals up to seven days for each milrinone-i.v. diluent mixture. Samples were examined visually and analyzed by high-performance liquid chromatography, enzymatic assay, or fluorescence polarization immunoassay. No precipitation or substantial pH change was observed in any of the mixtures. In all the mixtures, milrinone retained more than 96% of its initial concentration, and the other drugs retained more than 97% of their initial concentrations. Milrinone 400 microg/mL in 5% dextrose injection and 29 critical care drugs were stable for four hours at 22-23 degrees C during simulated Y-site administration. Milrinone 400 microg/mL was stable in lactated Ringer's injection, 5% dextrose injection, 0.45% sodium chloride injection, and 0.9% sodium chloride injection for seven days at 22-23 degrees C.     

Osmolality of small-volume intravenous admixtures

Osmolalities of commonly administered small-volume i.v. admixtures were determined, and use of diluents with lower osmolality to achieve osmolality values less than 400 mOsm/kg was studied. The theoretical osmolality of 218 hypothetical admixtures of various concentrations of 34 injectable drugs in 50- or 100-mL quantities of 5% dextrose injection or 0.9% sodium chloride injection was calculated using sodium chloride equivalents. If the calculated osmolality value was greater than 400 mOsm/kg, an actual admixture was prepared and osmolality and density were measured. To determine how admixtures with osmolality values less than 400 mOsm/kg could be prepared, theoretical osmolality was calculated using 0.45% sodium chloride injection or sterile water for injection as the diluent. The calculated osmolality value was greater than 400 mOsm/kg for 52 (23.9%) of the 218 admixtures tested. Of the 52 measured osmolality values, 47 were within 15% of the calculated value. Calculated osmolality values for all admixtures were less than 400 mOsm/kg when 0.45% sodium chloride injection or sterile water for injection was used as the diluent. Admixture osmolality should be considered when preparing drugs for i.v. injection. For drugs with high osmolalities, 0.45% sodium chloride injection or sterile water for injection may be used as the diluent.     

Stability of pibenzimol hydrochloride in commonly used infusion solutions and after filtration

The stability of pibenzimol hydrochloride was evaluated after reconstitution, after addition to several intravenous fluids, and after filtration. Vials containing pibenzimol hydrochloride 50 mg were reconstituted with 2.5 mL of 0.9% sodium chloride injection to 20 mg/mL. For determination of drug stability in intravenous fluids, vial contents were further diluted to 0.15 mg/mL by injection into glass containers and polyvinyl chloride (PVC) bags containing 250 mL of 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection. Pibenzimol concentrations were determined immediately after preparation and at various intervals after storage at 4-6 degrees C or 25 degrees C by means of a stability-indicating, high-performance liquid chromatographic technique. Vial contents were inspected visually for color changes, and pH was measured. Determinations were also made of the stability of pibenzimol 0.15 mg/mL in 0.9% sodium chloride injection after simulated infusions using a 0.22-micron filter set at 25 degrees C. All study solutions and admixtures retained more than 90% of the initial pibenzimol concentration. The greatest loss of drug (6-7%) occurred after 24 hours in lactated Ringer's injection in both glass and PVC containers and in 0.9% sodium chloride injection in PVC bags. No drug loss occurred as a result of filtration. Reconstituted pibenzimol hydrochloride and admixtures of pibenzimol in 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection in glass or PVC containers are stable for at least 24 hours at 25 degrees C. Filtration has no effect on stability.     

Stability of milrinone in 0.45% sodium chloride, 0.9% sodium chloride, or 5% dextrose injections

The stability of milrinone in 0.45% and 0.9% sodium chloride injections and in 5% dextrose injection in glass and plastic containers was studied. Admixtures containing milrinone 0.2 mg/mL were prepared in three 500-mL glass containers, three 500-mL polyethylpolypropyl copolymer plastic containers, and three 1-L flexible plastic containers of each solution. Milrinone content was determined by high-performance liquid chromatography at intervals during 72 hours of storage at room temperature; one sample of each solution and container type was protected from light. Duplicate assays of each sample were performed, and samples were observed for visual and pH changes. In all samples milrinone concentrations were more than 97% of the initial concentration. No changes in pH or appearance occurred. Milrinone at a concentration of 0.2 mg/mL is stable for 72 hours at room temperature in 0.45% and 0.9% sodium chloride injections and in 5% dextrose injection in glass or plastic containers.     

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 1: stability with common intravenous fluids.

The stability of dopamine hydrochloride (Intropin) in several large-volume parenteral solutions was studied. Admixtures of dopamine were assayed by colorimetric and chromatographic procedures. Admixtures (800 mug dopamine per ml) in the following intravenous fluids in glass bottles at pH 6.85 or below were found to be chemically and physically stable for at least 48 hours at room temperature: dextrose 5%, dextrose 5% and sodium chloride 0.9%, 5% dextrose in 0.45% sodium chloride, dextrose 5% in lactated Ringer's solution, lactated Ringer's injection, 0.9% sodium chloride, 1/6 molar sodium lactate, and 20% mannitol. The admixture of dopamine in 5% dextrose was stable for a minimum of seven days at 5 C. A 5% dextrose-dopamine admixture in a polyvinylchloride bag was stable for at least 24 hours at room temperature. The admixture of dopamine in 5% sodium bicarbonate solution produced an unstable solution of pH 8.20. A chemical and physical change (development of a pink color) was observed in this admixture. It is recommended that dopamine not be added to 5% sodium bicarbonate solution or any alkaline intravenous solution.     

Simulated Y-Site Compatibility of Vancomycin and Piperacillin-Tazobactam

Purpose:

To evaluate the physical compatibility of vancomycin with piperacillin-tazobactam during simulated Y-site administration.

Methods:

Vancomycin and piperacillin-tazobactam were tested using 2 different diluents: 0.9% sodium chloride and 5% dextrose for injection. Vancomycin concentrations of 2, 5, and 10 mg/mL were tested using 0.9% sodium chloride and 4 and 8 mg/mL in 5% dextrose. Piperacillin-tazobactam was diluted to 16, 30, 40, 80, and 100 mg/mL, representing common concentrations used clinically in hospitals, and concentrations were tested in both 0.9% sodium chloride and 5% dextrose for injection. Medications were reconstituted under USP <797> aseptic technique. Combinations were tested in duplicate and reverse order with control solutions. Compatibility testing for Y-site included visual inspection, inspection with a high-intensity monodirectional light source (Tyndall beam), turbidimeter for turbidity evaluation, pH, and microscopic viewing. Testing occurred immediately after mixing, 15 minutes, 60 minutes, and 4 hours. If inconsistencies were observed between samples, testing was repeated to confirm results. Solutions were deemed incompatible if any one test failed and compatible if all tests were accepted.

Results:

When dextrose 5% for injection was used as the diluent, vancomycin 4 mg/mL was Y-site compatible with piperacillin-tazobactam 16, 30, and 40 mg/mL and incompatible with 80 and 100 mg/mL. Vancomycin 8 mg/mL was incompatible with all tested concentrations of piperacillin-tazobactam. When 0.9% sodium chloride was used as the diluents, Y-site compatibility was found with vancomycin 2 and 5 mg/mL and all tested concentrations of piperacillin-tazobactam. Vancomycin 10 mg/mL was incompatible with piperacillin-tazobactam 40, 80, and 100 mg/mL. Incompatibilities formed a white precipitate immediately on mixing.

Conclusion:

Y-site incompatibility was greater for the tested concentrations of piperacillin-tazobactam and vancomycin when 5% dextrose was used as the diluent versus 0.9% sodium chloride. Y-site incompatibility was seen immediately in the form of a white precipitate on mixing.