The stability of docetaxel diluted to 0.3 or 0.9 mg/mL with 0.9% sodium chloride injection and stored in polyolefin or glass containers was studied.
Vials of docetaxel injection concentrate were reconstituted with the entire contents of the solvent vial and carefully homogenized to avoid the formation of foam. Solutions were aseptically prepared with nominal docetaxel concentrations of 0.3 and 0.9 mg/mL by adding the appropriate quantities to polyolefin containers or glass bottles, to which had been added the appropriate volume of 0.9% sodium chloride injection, yielding a final volume of 50 mL. Three identical polyolefin containers and one control glass bottle for each concentration were prepared. All test solutions were stored at 19-21 degrees C and protected from light. Chemical stability was measured by using a stability-indicating high-performance liquid chromatographic (HPLC) assay with ultraviolet-light detection. Physical stability was determined by visual inspection.
No evidence of precipitation was observed during the first 24 hours of the study. However, after a day of storage, the HPLC assay revealed large relative standard deviation values for diluted docetaxel solutions in some containers. These values were predictive for the formation of precipitates and compatible with the existence of microprecipitates at 24 hours. These results suggest that the diluted docetaxel infusions were not stable when stored at 19-21 degrees C.
Docetaxel 0.3 and 0.9 mg/mL in 0.9% sodium chloride injection was not physically stable for more than one day when stored at 19-21 degrees C. Docetaxel stability in diluted solutions appears sensitive to slight changes in temperature and degree of agitation.
The stability of metoprolol tartrate injection 1 mg/mL undiluted and 0.5 mg/mL in 0.9% sodium chloride injection and 5% dextrose injection was studied.
Sample set A contained 50 mL of Metoprolol Tartrate Injection, USP, 1 mg/mL transferred directly from the vials. Sample set B contained 50 mL of metoprolol 0.5 mg/mL diluted with 0.9% sodium chloride injection, and sample set C contained 50 mL of metoprolol 0.5 mg/mL diluted with 5% dextrose. All samples were prepared in triplicate and stored at room temperature. The stability of the samples was analyzed in duplicate using stability-indicating high-performance liquid chromatography immediately after preparation and at 6, 12, 18, 24, and 30 hours. The samples were assessed for pH and inspected for color and visible precipitation changes. The stability of metoprolol was determined by evaluating the percentage of the initial concentration remaining at each time interval. Stability of the product was defined as retention of 90% of the initial concentration.
The mean +/- S.D. initial concentration in sample sets A, B, and C was 1.006 +/- 0.009 mg/mL, 0.498 +/- 0.002 mg/mL, and 0.499 +/- 0.002 mg/mL, respectively. Throughout the 30-hour study period, at least 99% of the initial concentration of metoprolol tartrate remained in all three preparations at all time points. No appreciable changes in pH occurred. No changes in color and no visible precipitate or microbial growth were detected.
Metoprolol tartrate injection 1 mg/mL undiluted and 0.5 mg/mL in 0.9% sodium chloride injection and 5% dextrose injection were stable at room temperature for at least 30 hours.
The use of 0.9% sodium chloride injection with and without heparin sodium for maintaining peripheral indwelling intermittent-infusion devices (PIIIDs) in infants was studied.
In this double-blind study, children up to one year of age who had a 24-gauge PIIID through which a continuous i.v. infusion was no longer running were randomly assigned to have their PIIID capped with 0.9% sodium chloride injection with or without heparin sodium 10 units/mL. PIIIDs were capped every eight hours if no medications were administered; otherwise, they were capped after each dose of an i.v. drug.
The heparin group had 26 patients with 28 evaluable PIIIDs, and the 0.9% sodium chloride injection group had 32 patients with 46 evaluable PIIIDs. The two groups did not differ significantly in variables assessing the duration of PIIID use, reasons for removal of PIIIDs, mean number of cappings, irritant potential of administered drugs, or severity of medication-related irritation.
There was no significant difference between 0.9% sodium chloride injection with and without heparin sodium 10 units/mL in maintaining 24-gauge PIIIDs in children younger than one year.
The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday Practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP&PRIME; s manuscript checklist. The text should be concise, and the number of references, tables, and figures should be limited.
The stability of fentanyl 5 microg/mL in 0.9% sodium chloride solution packaged in polypropylene syringes was studied.
Samples of fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection were prepared and assessed for chemical stability using a validated, stability-indicating high- performance liquid chromatographic (HPLC) assay. A total of 12 syringe samples were submitted for chemical stability testing by HPLC. The syringes were protected from light and stored in controlled ambient conditions (23-27 degrees C and 55-65% relative humidity) in an environmental chamber. Three samples were tested initially and at each 30-day interval. Each syringe sample was tested with two determinations, using the average of the determinations for the assay result. Samples were assessed for pH and inspected for color and visible particulate matter. Stability was defined as the retention of 90-110% of the initial drug concentration at 30, 60, and 90 days.
Fentanyl citrate injection maintained the appearance of a clear, colorless solution, with mean +/- S.D. pH values ranging from 4.13 +/- 0.01 to 4.52 +/- 0.02 throughout the study period. Recovery of fentanyl ranged from 99.86% +/- 0.29% to 102.74% +/- 1.60% of the initial concentration, with no detectable changes in the chromatographic profiles of all tested samples.
Fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection, packaged in polypropylene syringes and stored protected from light, was stable for at least 90 days in controlled ambient conditions.
The compatibility and stability of butorphanol tartrate and droperidol in polyvinyl chloride (PVC) bags and glass bottles stored at 4°C and 25°C for up to 15 days were studied.
Admixtures were assessed initially and for 15 days after preparation in PVC bags and glass bottles using 0.9% sodium chloride injection as a diluent and stored at 4°C and 25°C. The initial drug concentrations were 0.08 mg/mL for butorphanol tartrate and 0.05 mg/mL for droperidol. Samples were withdrawn from each container immediately after preparation and at predetermined intervals (2, 4, 8, 24, 48, 72, 120, 168, 240, and 360 hours after preparation). The solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using a validated high-pressure liquid chromatography method.
After 15 days of storage, all formulations tested retained >98% of the initial concentrations of both drugs. The drug mixtures were clear in appearance, and no color change or precipitation was observed. Throughout this period, pH values remained stable.
Admixtures of butorphanol tartrate 0.08 mg/mL and droperidol 0.05 mg/mL in 0.9% sodium chloride injection were stable for at least 360 hours when stored in PVC bags or glass bottles at 4°C and 25°C and protected from light. AM J HEALTH-SYST PHARM: 2013; 70:515-9.
Voriconazole injection 2 mg/mL, when protected from light, was stable for eight days when stored at 4 or 25 °C in 0.9% sodium chloride injection, six days at 4 °C in 5% dextrose injection, and four days at 25 °C in 5% dextrose injection.
The stability of thiotepa in a new formulation of the drug was studied.
Vials of Thioplex (Immunex), a relatively new lyophilized formulation of thiotepa, were reconstituted with sterile water and diluted with 0.9% sodium chloride injection in polyvinyl chloride infusion bags to thiotepa concentrations of 0.5, 1, and 3 mg/mL. The solutions were stored at 8 and 25 °C in ambient light and analyzed at 0, 8, 24, and in most cases 48 hours for thiotepa concentration and chloro-adduct formation by stability-indicating high-performance liquid chromatography.
Thiotepa 1 and 3 mg/mL was stable for 48 hours at 8 °C and for 24 hours at 25 °C.
Thiotepa 0.5 mg/mL was not stable at either temperature. Storage at 8 °C slowed but did not prevent chloro-adduct formation and loss of potency. The pH tended to increase with time; turbidity remained low. Thiotepa (lyophilized) 1 and 3 mg/mL in 0.9% sodium chloride injection was stable for 48 hours at 8 °C and for 24 hours at 25 °C; the drug was unstable when diluted to 0.5 mg/mL and stored under the same conditions.
The stability of enoxaparin sodium in 0.9% sodium chloride injection in polyvinyl chloride (PVC) containers was studied.
Triplicate solutions of 120 mg (1.2 ml) of enoxaparin (as the sodium salt) and 98.8 mL of 0.9% sodium chloride injection were prepared in 250-mL PVC containers and stored at room temperature (20-22 °C). Samples were taken immediately after preparation and at 0.25. 0.3, 0.75, 1, 4. 12, 16. 24, and 48 hours. Inspections for color change and precipitation were performed with a clarity inspection station and a magnifying glass. Samples of the three admixtures were evaluated in duplicate for pharmacologic activity by an automated coagulation heparin assay.
Throughout the 48-hour study period, the enoxaparin admixtures were free of color change, evolution of gas. and precipitates. The pharmacologic activity of enoxaparin in the PVC containers remained >94% of the initial measured activity for 48 hours.
Enoxaparin 1.2 mg/ml. (as the sodium salt) in 0.9% sodium chloride injection in PVC containers was stable for up to 48 hours at 20-22 °C.
The stability of dexmedetomidine in polyvinyl chloride (PVC) bags containing 0.9% sodium chloride injection was studied.
Dexmedetomidine solutions (4, 8, 12, and 20 μg/mL; n = 6 for each) were prepared by removing 2, 4, 6, and 10 mL of 0.9% sodium chloride injection, respectively, from 50-mL PVC bags and injecting 2, 4, 6, and 10 mL of dexmedetomidine 100 μg/mL, respectively. To ensure a homogeneous mixture, the contents of each bag was manually mixed initially and before each sample was removed. All compounding was conducted by a single pharmacist using aseptic technique in a horizontal-laminar-airflow hood at 25 °C. Forced-degradation studies were conducted at 70 ± 1 °C. Stability samples were analyzed using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry (LC/MS-MS) and high-performance liquid chromatography-ultraviolet-light (HPLC/UV) absorbance. Forced-degradation samples were monitored using LC/MS-MS, HPLC/UV, and gas chromatography-MS.
Dexmedetomidine solutions were very stable at 23 ± 2 °C at all four concentrations over the 48-hour testing period. As determined via LC/MS-MS and HPLC/UV methods, over 97% of the initial concentration of dexmedetomidine remained after 48 hours. Extensive HPLC/UV active degradation products could be observed in basic conditions; only minor UV active degradation products were observed in acidic, oxidative, and photochemical conditions.
Dexmedetomidine hydrochloride 4, 8, 12, and 20 μg/mL stored in PVC bags at 23 ± 2 °C was stable for 48 hours, despite a slight decrease in solution pH seen with increasing dexmedetomidine concentrations.
The stability of polymyxin B sulfate in infusion bags containing 0.9% sodium chloride injection stored at 4 and 25 degrees C was studied.
Seven manufacturing batches of polymyxin B from different sources were tested. The products were reconstituted in sterile water for injection, diluted in infusion bags containing 0.9% sodium chloride injection, and stored at room temperature (25 degrees C) or under refrigeration (4 degrees C). Samples were withdrawn at the same time on days 0, 1, 2, 3, 5, and 7. A modified microbiological assay was used to determine the concentrations, as indicated by zones of inhibition, of polymyxin B. Bordetella bronchiseptica served as the reference organism. Stability was defined as retention of >90% of the initial concentration. The decomposition kinetics of polymyxin B in 0.9% sodium chloride injection were evaluated by plotting the polymyxin B concentration remaining versus time.
On average, the samples retained over 90% of their initial concentration for up to two days at both storage temperatures. All samples retained over 90% of their initial concentration at 24 hours. The decomposition kinetics of polymyxin B in infusion bags containing 0.9% sodium chloride injection exhibited pseudo-first-order kinetics, with rate constants of 0.024-0.075 day(-1) at 25 degrees C and 0.022-0.043 day(-1) at 4 degrees C (p > 0.05).
Polymyxin B was stable for at least one day when stored at 4 or 25 degrees C in infusion bags containing 0.9% sodium chloride injection. Stability did not differ significantly between the two storage temperatures.
Cyclosporine is a potent immunosuppressive agent used to reduce the risk of rejection after allogenic organ transplantations and for the treatment of chronic organ rejection in patients previously treated with other immunosuppressive agents. I.V. cyclosporine for injection contains cyclosporine,
The stability of penicillin G sodium solutions stored in polyvinyl chloride (PVC) bags or elastomeric pump containers was studied.
Test samples were prepared by diluting powdered penicillin G sodium (10 million units/10-mL vial) to solutions of 2,500 or 50,000 units/mL with 0.9% sodium chloride injection or 5% dextrose injection. The preparations were transferred to 250-mL PVC bags and elastomeric pump containers. All samples were prepared in triplicate and stored at 5°C. Chemical stability was measured by a stability-indicating high-performance liquid chromatographic (HPLC) assay and by pH evaluation. Particulate matter was evaluated according to compendial standards using a light-obscuration particle count test. Preparations were visually examined throughout the study.
After 21 days of storage, all test samples remained chemically stable, with an HPLC assay recovery value of more than 90% of the initial value. After 28 days, all samples prepared with either diluent and stored in PVC bags, as well as the samples diluted to 2,500 units/mL with sodium chloride injection and stored in elastomeric pump containers, did not meet the recovery acceptance limit. For all test samples, the mean pH consistently decreased during storage, from about 6.4 to about 5.5. Particle counts remained acceptable throughout the study, and no change in appearance was observed.
Penicillin G for injection (2,500 and 50,000 units/mL) diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored at 5°C in PVC containers or elastomeric pump containers was physically and chemically stable for a period of at least 21 days.
Patient safety “improved slightly” from 2000 to 2005 yet other areas of health care improved “at significantly greater rates,” the federal Agency for Healthcare Research and Quality (AHRQ) announced in March.
The fifth annual National Healthcare Quality Report states that patient safety
Total payments to acute care hospitals for inpatient care provided to Medicare beneficiaries in fiscal year 2006 will increase by $3.3 billion over fiscal year 2005, according to an estimate from the Centers for Medicare and Medicaid Services (CMS).
The revised payment rates and other changes to
The contamination rates associated with the preparation of medium-risk i.v. admixtures in a traditional practice site and in a class 1000 cleanroom were compared.
Simulated product media fills served as the samples. Each investigator, a pharmacist and a pharmacy technician, prepared 500 vials and 500 small-volume parenteral (SVP) bags in five separate runs at a traditional practice site and in a cleanroom. United States Pharmacopeia chapter 797 medium-risk compounding procedures were followed, and strict adherence to aseptic technique was employed. Single-strength tryptic soy broth was substituted for the drug and diluent in the admixtures. Positive and negative controls were also prepared and stored for the duration of the study. The pharmacist and technician prepared a total of 4057 samples: 2027 samples (1014 vials and 1013 SVP bags) were prepared in a class 1000 cleanroom, and 2030 (1014 vials and 1016 SVP bags) were prepared at a traditional practice site.
Contamination rates did not significantly differ between the traditional practice site (0.296%) and the cleanroom environment (0.344%) (p = 1.0). A significant difference in the number of contaminated samples was found between the two investigators (2 of 2057 were contaminated by the pharmacist and 11 of 2000 were contaminated by the technician) (p = 0.012). Contamination rates by the pharmacist (p = 1.0) and technician (p = 1.0) did not significantly differ between sites.
The most important variable affecting microbial contamination of admixtures was the aseptic technique of personnel, not the environment in which the drugs were compounded.
An interface is an exchange of information between two computer programs that typically run on different computer systems.1 Interfaces are useful when information generated by one computer program (e.g., a patient registration system) can be used to replace manual data entry on another program (e.g
Captain Arthur W. Dodds, Sr., president of ASHP in 1966–67 and a former chief of pharmacy services in the U.S. Public Health Service (PHS), died on July 30 of natural causes near his home in Silver Spring, Maryland. He was 102.
A 22-year member of the PHS Commissioned Corps, Dodds received the
The permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions is described.
Thirteen cytotoxic agents were prepared at the highest concentrations normally encountered by pharmacy personnel. Four glove types--neoprene, natural rubber latex, nitrile, and vinyl--were exposed to the cytotoxic agents for 15, 30, and 60 minutes. Tests were conducted using the middle finger of each glove. Linearity, reproducibility, and sensitivity were evaluated for each drug tested. Assays were run using liquid chromatographic tandem mass spectrometry (LC/MS/MS) and high-performance liquid chromatography with ultraviolet light (HPLC-UV). Permeability testing was conducted using an original system designed to evaluate dynamic constraints, such as rubbing, stretching, and tension.
Linearity by LC/MS/MS and HPLC-UV was confirmed at concentrations up to 1000 ng/mL for all drugs. Most glove materials were permeable at rates below ASTM recommendations over the one-hour testing period. Vinyl was the most permeable material. Carmustine permeated the widest variety of materials. Due to the high sensitivity of the analytic methods, all materials displayed low but significant permeability for at least one drug after one hour. Higher resistance to permeation was recorded for all neoprene, some natural rubber latex, and one nitrile glove.
Neoprene, natural rubber latex, and nitrile gloves displayed the highest resistance to permeation of the 13 cytotoxic agents studied. Additional factors, such as duration of exposure, glove thickness, and drug liposolubility and molecular weight, also affected permeability.
The rationale for clinical trials of antiestrogens for prevention of breast cancer, potential concerns with antiestrogens, and clinical trials of antiestrogens for breast cancer prevention are discussed. Extensive preclinical evidence supports clinical investigation and use of tamoxifen for preventing breast cancer. The efficacy of tamoxifen in the treatment of advanced breast cancer and as adjuvant therapy has further strengthened the rationale for use in prevention. Tamoxifen is well tolerated and, like raloxifene, has been associated with non-cancer-related benefits. The major concerns with tamoxifen are an increased risk of thromboembolic events and endometrial cancer and an association with ocular disorders. Little is known about the long-term safety of raloxifene. Three randomized, double-blind, placebo-controlled clinical trials of tamoxifen 20 mg (as the citrate) daily for the prevention of breast cancer and one post hoc analysis and a literature review examining the effect of raloxifene on breast cancer risk (as a secondary endpoint) have been published. In one of the three trials of tamoxifen, the rate of invasive breast cancer was reduced 49%; in the other two trials, no reduction in breast cancer was found. Raloxifene apparently reduced the frequency of breast cancer. On the basis of the positive tamoxifen trial, tamoxifen can be offered to women with a five-year projected risk of breast cancer of > or = 1.67%, as determined by the Gail model. Risks and benefits should be evaluated for each patient. Tamoxifen may offer some women protection against breast cancer. Raloxifene may also have a preventive role, but more study is needed.
Charter member Leo F. Godley, M.S., who served ASHP at its highest levels and received the Society’s highest honor, died May 22 at his home in Fort Worth, Texas. He was 93 years old.
Leo F. Godley, when he was named the 1969 Harvey A. K. Whitney Lecture Award recipient
The terms mentor and preceptor are often used interchangeably. However, these two very important roles have defining features that make them quite different. The relationship between a mentor and mentee is a “naturally formed, one-on-one, mutual, committed, nonsexual relationship between a junior
Drug-drug, drug-food, and drug-disease interactions involving hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are reviewed. The four available HMG-CoA reductase inhibitors-lovastatin, simvastatin, pravastatin, and fluvastatin-have different potentials for drug interactions, probably because of their different pharmacokinetic characteristics. Interactions of some of these cholesterol-lowering agents with cyclosporine, erythromycin, high-dose niacin, or gemfibrozil may produce myopathy with or without rhabdomyolysis. Interactions with other commonly prescribed agents, such as bile acid sequestrants, coumarin anticoagulants, and cardiovascular drugs, may alter the pharmacokinetics of either drug, but the clinical significance is generally minor. Food may affect plasma lovastatin concentrations, systemic pravastatin bioavailability, and the maximum serum concentration (Cmax) and time to achieve Cmax for fluvastatin. Hepatic dysfunction may influence the pharmacokinetics of pravastatin; all HMG-CoA reductase inhibitors are contraindicated in patients with liver disease or unexplained elevations in serum aminotransferases. Severe renal insufficiency may necessitate dosage modification in lovastatin recipients. Renal dysfunction seems to affect the pharmacokinetics of pravastatin, simvastatin, and fluvastatin only minimally, but caution is still warranted. Although the HMG-CoA reductase inhibitors rarely have severe adverse effects, they may interact, in some cases dangerously, with other drugs, with food, and with disease states.