Stability of milrinone and digoxin, furosemide, procainamide hydrochloride, propranolol hydrochloride, quinidine gluconate, or verapamil hydrochloride in 5% dextrose injection

The stability of milrinone and digoxin, furosemide, procainamide hydrochloride, propranolol hydrochloride, quinidine gluconate, or verapamil hydrochloride in 5% dextrose injection containing milrinone was studied. Milrinone admixtures with digoxin, furosemide, propranolol hydrochloride, quinidine gluconate, and verapamil hydrochloride were studied at two concentrations. Admixtures of milrinone and procainamide hydrochloride were studied at four concentrations. Duplicate solutions of each admixture and each control were prepared and stored in glass containers for four hours at room temperature (22-23 degrees C), under normal fluorescent lights. The samples were analyzed immediately by visual inspection, tested for pH, and assayed by high-performance liquid chromatography (HPLC). Milrinone 0.35 mg/mL-furosemide 4 mg/mL and milrinone 0.1 mg/mL-furosemide 5 mg/mL admixtures precipitated immediately after preparation and were not studied by HPLC. No changes in pH or visual appearance were observed in the remaining admixtures after storage at room temperature for four hours. Admixtures containing milrinone 0.175 or 0.2 mg/mL and procainamide hydrochloride 1, 2, or 4 mg/mL satisfied the USP standard for procainamide hydrochloride injection USP assay after one hour but failed this test in all cases after four hours. No degradation of milrinone was observed in any of the admixtures containing procainamide hydrochloride. Milrinone and furosemide are incompatible in 5% dextrose injection and should be administered separately. The remaining admixtures were compatible, and all except those containing procainamide hydrochloride were stable for four hours at room temperature.     

Stability of amiodarone hydrochloride in admixtures with other injectable drugs

The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.     

Stability and compatibility of tirofiban hydrochloride during simulated Y-site administration with other drugs.

The stability and compatibility of tirofiban hydrochloride injection during simulated Y-site administration with various other drugs were studied. Tirofiban hydrochloride, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, and propranolol hydrochloride injections were each prepared from their respective concentrates in both 0.9% sodium chloride injection and 5% dextrose injection at both the minimum and maximum concentrations normally administered. The high-concentration solutions of midazolam hydrochloride and furosemide were used as is. Morphine sulfate was diluted in 5% dextrose injection only. Nitroglycerin premixed infusions, atropine sulfate injection, and diazepam injection were used as is. Tirofiban hydrochloride solutions were combined 1:1 with each of the secondary drug solutions in separate glass containers. Samples were stored for four hours at room temperature under ambient fluorescent light and were assayed for drug content and degradation by high-performance liquid chromatography and for pH, appearance, and turbidity. All mixtures except those containing diazepam remained clear and colorless, with no visual or turbidimetric indication of physical instability. Mixing of tirofiban hydrochloride and diazepam solutions resulted in immediate precipitation. all remaining mixtures remained clear. There was no significant loss of any of the drugs tested, no increase in known degradation products, and no appearance of unknown drug-related peaks. The pH of all test solutions remained constant. Tirofiban hydrochloride injection 0.05 mg/mL was stable for at least four hours when combined 1:1 in glass containers with atropine sulfate, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, morphine sulfate, nitroglycerin, and propranolol hydrochloride at the concentrations studied. Tirofiban hydrochloride was incompatible with diazepam.     

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.     

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.     

Compatibility of heparin sodium and morphine sulfate

The compatibility of morphine sulfate and heparin sodium was studied in solutions of deionized water and 0.9% sodium chloride. Crystalline morphine sulfate was reconstituted and heparin sodium 100 or 200 units/mL was added. Duplicate samples with a final volume of 5 mL were prepared and stored at room temperature. Morphine sulfate concentrations were 1, 2, 5, and 10 mg/mL in each diluent with each heparin concentration. Samples were visually inspected immediately after preparation and at 0.5 and 24 hours; pH was tested before adding heparin and at 0.5 and 24 hours. Similar procedures were followed adding morphine to the heparin. Samples containing morphine sulfate 2 and 10 mg/mL were analyzed by high-performance liquid chromatography for morphine concentrations immediately before adding heparin and at 0.5 and 24 hours. Precipitate appeared immediately after the second drug was added in samples containing morphine sulfate 10 mg/mL at both heparin concentrations in the water admixtures. No precipitate formed in any solutions containing morphine concentrations of 5 mg/mL or less nor in any samples containing 0.9% sodium chloride. In both diluents, pH values decreased as morphine sulfate concentrations increased. Morphine sulfate concentrations decreased significantly in water admixtures but not in admixtures prepared with 0.9% sodium chloride solution. Morphine sulfate and heparin sodium are incompatible only at morphine concentrations greater than 5 mg/mL. The incompatibility can be prevented by using 0.9% sodium chloride as the admixture 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 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.     

Sorption of various drugs in polyvinyl chloride, glass, and polyethylene-lined infusion containers

The sorption of chloroquine sulfate, diazepam, isosorbide dinitrate, lorazepam, midazolam, nitroglycerin, promethazine hydrochloride, thiopental sodium, and warfarin sodium to three types of containers was studied. Appropriate amounts of the drugs were added to 500 mL of 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags, glass bottles, and Clear-Flex bags composed of a laminate of polyethylene, nylon, and polypropylene. The containers were stored in the dark at room temperature for 24 hours. Samples were taken at various intervals and assayed for drug concentration by high-performance liquid chromatography. There were no appreciable changes in pH after 24 hours, and all the admixtures remained clear and colorless. The potency of chloroquine sulfate, lorazepam, midazolam, promethazine hydrochloride, and thiopental sodium remained unchanged in glass, PVC, and Clear-Flex containers. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium did not show any sorption to glass bottles and Clear-Flex bags. In PVC bags, however, up to 55% of diazepam, 23% of isosorbide dinitrate, 51% of nitroglycerin, and 24% of warfarin sodium was lost during the 24-hour study period. Diazepam, isosorbide dinitrate, nitroglycerin, and warfarin sodium in 0.9% sodium chloride injection showed a loss of potency when stored in PVC containers for 24 hours at room temperature, but none of the drugs studied lost potency when stored in glass bottles and Clear-Flex bags.     

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.     

Compatibility of clindamycin phosphate with cefotaxime sodium or netilmicin sulfate in small-volume admixtures

The stability and compatibility of clindamycin phosphate plus either cefotaxime sodium or netilmicin sulfate in small-volume intravenous admixtures were studied. Admixtures containing each drug alone and two-drug admixtures of clindamycin phosphate plus cefotaxime sodium or netilmicin sulfate were prepared in 100 mL of 5% dextrose injection and 0.9% sodium chloride injection in both glass bottles and polyvinyl chloride (PVC) bags. Final concentrations of clindamycin, cefotaxime, and netilmicin were 9, 20, and 3 mg/mL, respectively. All solutions were prepared in duplicate and stored at room temperature (24 +/- 2 degrees C). Samples were visually inspected, tested for pH, and assayed for antibiotic concentration using stability-indicating assays at 0, 1, 4, 8, 16, and 24 hours for admixtures in glass bottles and at 0, 8, and 24 hours for admixtures in PVC bags. No substantial changes in color, clarity, pH, or drug concentration were observed in any of the solutions. Clindamycin phosphate is compatible with cefotaxime sodium or netilmicin sulfate in 5% dextrose and 0.9% sodium chloride injections in glass bottles or PVC bags for 24 hours.     

EPOCH方案中依托泊苷、盐酸多柔比星和硫酸长春新碱的配伍稳定性

目的：考察EPOCH方案中3种药物在0.9%氯化钠溶液中的配伍稳定性,为临床使用该方案提供理论依据。方法：模拟临床给药浓度配制EPOCH方案混合输液,其中依托泊苷（VP-16）质量浓度为175 μg·mL^-1,盐酸多柔比星（ADM）质量浓度为35 μg·mL^-1,硫酸长春新碱（VCR）质量浓度为1.4 μg·mL^-1,用高效液相色谱法测定混合输液36 h内的各成分含量及不溶性微粒数变化,pH计测定pH值。结果：所建立的HPLC检测方法简单,可靠,稳定,应用此法对EPOCH方案中配伍的3种药物浓度和pH进行检测,结果显示3种成分的浓度和溶液的pH值在36 h内基本未发生变化。结论：EPOCH方案中3种化疗药物按照临床使用浓度配伍,在500 mL生理盐水中相容且稳定,此配伍输注方法临床应用安全可靠。     

Physical and chemical stability of palonosetron hydrochloride with five opiate agonists during simulated Y-site administration.

PURPOSE: The physical and chemical compatibility of palonosetron hydrochloride with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration was studied. METHODS: Test samples were prepared in triplicate by mixing 7.5-mL samples of undiluted palonosetron 50 microg/mL (of palonosetron) with 7.5-mL samples of fentanyl citrate 50 microg/mL, morphine sulfate 15 mg/mL, hydromorphone hydrochloride 0.5 mg/mL, meperidine hydrochloride 10 mg/mL, and sufentanil citrate 12.5 microg/mL (of sufentanil) per milliliter individually in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. RESULTS: All of the admixtures were initially clear and colorless in normal fluorescent room light and when viewed with a high-intensity monodirectional light (Tyndall beam) and were essentially without haze. Changes in turbidity were minor throughout the study. Particulates measuring 10 microm or larger were few in all samples throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the opiate agonists tested over the four-hour period. Similarly, little or no loss of the opiate agonists occurred over the four-hour period. CONCLUSION: Palonosetron hydrochloride was physically and chemically stable with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration.     

Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures.     

Interaction of aztreonam with nafcillin in intravenous admixtures

An interaction between aztreonam and nafcillin sodium in 0.9% sodium chloride injection or 5% dextrose injection stored in glass or plastic containers is reported. During preliminary experiments, admixtures of aztreonam 10 or 20 mg/mL and nafcillin sodium 10 or 20 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection prepared in glass flasks became cloudy and showed evidence of a fine precipitate. Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) assay. Admixtures of aztreonam 20 mg/mL and nafcillin sodium 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared in polyvinyl chloride bags and stored at room temperature (23-25 degrees C) for 48 hours. The admixtures were assayed at 0, 24, and 48 hours with the same HPLC procedure used during the pretesting experiments. The precipitates were isolated, washed, and centrifuged; the supernatant was analyzed by HPLC assay, and the final residue was analyzed by nuclear magnetic resonance (NMR) spectroscopy. The initial recoveries of drug from the pretesting experiments ranged from 99.2 to 102.4%. Analysis of the precipitates indicated that the precipitate was neither a salt nor a complex formed by the physical interaction of aztreonam and nafcillin sodium, but probably a high-molecular-weight polymer formed by the covalent bonding of subunits of the formulation components. Substantial losses of both drugs from the admixtures were evident after 48 hours of storage. The precipitate was observed sooner in the admixtures containing 0.9% sodium chloride injection than in the admixtures prepared in 5% dextrose injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Compatibility of verapamil hydrochloride with penicillin admixtures during simulated Y-site injection

The compatibility of verapamil hydrochloride during simulated Y-site injection with i.v. admixtures containing 11 different penicillins was studied. Admixtures of penicillin G potassium (62.5 mg/mL), nafcillin sodium (40 mg/mL), oxacillin sodium (40 mg/mL), ampicillin sodium (40 mg/mL), carbenicillin disodium (40 mg/mL), methicillin sodium (40 mg/mL), ticarcillin sodium (40 mg/mL), azlocillin sodium (40 mg/mL), mezlocillin sodium (40 mg/mL), piperacillin sodium (40 mg/mL), and amdinocillin (20 mg/mL) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Verapamil hydrochloride injection 4 mL (10 mg) was then added to each admixture, and the admixtures were examined macroscopically and microscopically for precipitate immediately and at 15 minutes and 24 hours after mixing. To simulate Y-site injection of verapamil, verapamil hydrochloride injection 1 mL (2.5 mg) was added to 1 mL of each penicillin admixture in a test tube. For admixtures in which precipitates formed, the pH was recorded before and after verapamil was added to the admixtures. Loss of verapamil hydrochloride when mixed with the penicillin admixtures was determined using reverse-phase high-performance liquid chromatography. Addition of verapamil hydrochloride to admixtures containing nafcillin sodium, oxacillin sodium, ampicillin sodium, and mezlocillin sodium resulted in substantial loss of verapamil hydrochloride. The results for the Y-site injection study showed visible precipitation with the same penicillin admixtures. Because a precipitate formed when verapamil hydrochloride was added to nafcillin sodium, oxacillin sodium, ampicillin sodium, or mezlocillin sodium in the diluents studied, we recommended that verapamil hydrochloride be administered separately or that the i.v. tubing be flushed thoroughly before and after this drug is administered through a Y-injection site with these penicillin admixtures.     

Stability of morphine sulfate in infusion devices and containers for intravenous administration

The stability of morphine sulfate in one brand of polyvinyl chloride (PVC) container, one brand of glass syringe, and two brands of disposable infusion devices was determined. Solutions of morphine sulfate 2 and 15 mg/mL were used to fill the PVC containers and drug administration devices. Stability was determined for both concentrations of morphine sulfate at room temperature (23-25 degrees C) and 4 degrees C in the PVC containers, glass syringes, and disposable infusion devices; stability was also determined at 31 degrees C in the disposable infusion devices. At 0, 1, 2, 4, 7, 12, and 15 days, portions of the solutions were removed and assayed in triplicate by a stability-indicating high-performance liquid chromatographic method. At each time point the drug-infusion fluid combinations were inspected visually for color changes and the presence of particulate matter, and pH was measured. Morphine sulfate 2 and 15 mg/mL remained stable for at least 12 days in all the containers and devices at each temperature tested. No substantial changes in the pH or physical appearance of the solutions were observed. Morphine sulfate can be repackaged in the disposable glass syringe, PVC container, and both disposable infusion devices for routine clinical use.     

Effect of procaine on the pH of buffered and unbuffered cardioplegic solutions

Changes in pH values were studied in two types of cardioplegic admixtures containing procaine 0.95 meq/L: an institutional formulation based on Ringer's injection and buffered with tromethamine injection 3.6%, and Plegisol (Abbott Laboratories) buffered with sodium bicarbonate injection 8.4%. Initial pH was measured in the buffered and unbuffered solutions before the addition of procaine and after the addition of 13 mL of procaine hydrochloride injection 2% or 260 mg of procaine hydrochloride powder (reference standard). Buffered 1-L admixtures containing procaine hydrochloride injection were stored (the institutional formulations in glass and the Plegisol admixtures in flexible plastic bags) at 3-5 degrees C or 25 degrees C. Plegisol admixtures were prepared with 10 mL (10 meq or 840 mg) of buffer as directed by the manufacturer or with 3 mL (3 meq) of buffer. Admixture pH was tested after various time intervals. Of the unbuffered solutions containing procaine, pH values were lower in Plegisol than in the institutional formulation. Of the procaine-containing buffered Plegisol solutions, only the admixture containing 3.0 mL of buffer and procaine prepared from powder had an initial pH in the acceptable range of 7.30-7.60. In all the stored solutions, pH changed rapidly; solution pH changed less under refrigeration. In the stored institutional admixtures, pH was acceptable for 96 hours at 3-5 degrees C and 24 hours at 25 degrees C. In the stored Plegisol admixtures to which 10 mL of buffer was added, pH was greater than 7.6 initially and continued to increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of hydroxyzine hydrochloride, meperidine hydrochloride and atropine sulfate in glass and plastic syringes.

The apparent stability of combinations of hydroxyzine hydrochloride and meperidine hydrochloride (50 mg/2 ml each) and of these two drugs (50 mg/2.5 ml each) and atropine sulfate (0.4 mg/2.5 ml) in prefilled glass and plastic syringes was studied. Syringes (3 ml) containing the combinations were stored at 25 C and 3 C for 10 days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined in addition to visual inspection. Results of these qualitative tests indicated that the mixtures apparently were stable for 10 days at room temperature or when refrigerated. No differences were found between solutions stored in glass and those stored in plastic syringes. Degradation of the syringe contents or appearance of additional constituents was not detected in any of the admixtures, and they were considered to be chemically compatible within the limitations of the study. The study suggests that storage of these combinations in syringes is feasible but the results cannot be extrapolated to drug solutions or syringes other than those studied.     

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.