Thomas C. Kupiec

Compatibility of ceftobiprole medocaril with selected drugs during simulated Y-site administration.

PURPOSE The physical compatibility of the new cephalosporin ceftobiprole medocaril with 70 other drugs during simulated Y-site injection was studied. METHODS Ceftobiprole was reconstituted with sterile water for injection. Dilutions of ceftobiprole 2 mg/mL (as ceftobiprole medocaril 2.67 mg/mL) were prepared in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringers injection. For testing compatibility with the other drugs, a 5-mL sample of the ceftobiprole 2-mg/mL admixtures was combined with a 5-mL sample of the other drug either undiluted or diluted with one of the three vehicles. Each combination was prepared in duplicate, switching the order of drug addition, and kept at room temperature. At intervals up to four hours after preparation, samples were examined visually and with the aid of a Tyndall beam and measured with a turbidimeter and a particle sizer and counter. Compatibility with propofol was evaluated by checking for emulsion separation and particles after centrifugation. RESULTS In all three vehicles, ceftobiprole was compatible with 31 other drugs and incompatible with 32. With 7 drugs, compatibility was dependent on the vehicle used. Signs of incompatibility included the presence of visible and subvisible particles, haze, and turbidity. No incompatibilities were related to the order of mixing. CONCLUSION Of the 70 drugs evaluated for compatibility with ceftobiprole 2 mg/ mL (as medocaril) in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringers injection, 31 were found to be compatible and 32 were found to be incompatible in all three of the infusion solutions. For 7 of the drugs, compatibility was dependent on which infusion solution was used. Ceftobiprole medocaril should not be simultaneously administered via a Y site with drugs with which it was shown to be incompatible.

Stability of fentanyl 5 μg/mL diluted with 0.9% sodium chloride injection and stored in polypropylene syringes

PURPOSE The stability of fentanyl 5 microg/mL in 0.9% sodium chloride solution packaged in polypropylene syringes was studied. METHODS 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. RESULTS 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. CONCLUSION 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.

Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients

ABSTRACT A stage I non-small cell lung cancer (NSCLC) serum profiling platform is presented which is highly efficient and accurate. Test sensitivity (0.95) for stage I NSCLC is the highest reported so far. Test metrics are reported for discriminating stage I adenocarcinoma vs squamous cell carcinoma subtypes. Blinded analysis identified 23 out of 24 stage I NSCLC and control serum samples. Group-discriminating mass peaks were targeted for tandem mass spectrometry peptide/protein identification, and yielded a lung cancer phenotype. Bioinformatic analysis revealed a novel lymphocyte adhesion pathway involved with early-stage lung cancer.

Physical and Chemical Stability of Esomeprazole Sodium Solutions

Background Esomeprazole sodium (Nexium IV, AstraZeneca) is the S-isomer of omeprazole and acts as a proton pump inhibitor gastric antisecretory agent indicated for the short-term treatment of gastroesophageal reflux disease in patients with a history of erosivo esophagitis. Currently, there is no information on the long-term stability of esomeprazole sodium in infusion solutions beyond 12 hours. Objective To evaluate the stability of esomeprazole sodium in 5% dextrose, 0,9% sodium chloride, and lactated Ringers injection, at 2 concentrations, at room temperature and when refrigerated. Methods Triplicate samples of esomeprazole 0.4 and 0.8 mg/mL as the sodium salt were prepared in the solutions required. Stability evaluations were performed initially, over 2 days stored at 23 °C, and over 5 days stored at 4 °C. Physical stability was assessed using turbidimetric and particulate measurement, as well as visual observation. Chemical stability was evaluated by stability-indicating high-performance liquid chromatography. Results: The samples in all 3 infusion solutions were physically stable throughout the study. None of the samples had evidence of visible haze or particulates. Most samples developed a slight yellow discoloration within 24 hours, but this discoloration was not accompanied by an excessive loss of drug content. The esomeprazole sodium samples in all 3 infusion solutions exhibited less than 7% loss over 2 days at 23 °C and over 5 days at 4 °C. Conclusions: Esomeprazole 0.4 and 0.8 mg/mL as the sodium salt in the infusion solutions tested is chemically and physically stable for at least 2 days at room temperature and 5 days under refrigeration.

Distinguishing Patients with Stage I Lung Cancer Versus Control Individuals using Serum Mass Profiling

Serum mass profiling can discern physiological changes associated with specific disease states and their progression. Sera (86 total) from control individuals and patients with stage I nonsmall cell lung cancer or benign small pulmonary nodules were discriminated retrospectively by serum changes discerned by mass profiling. Control individuals were distinguished from patients with Stage I lung cancer or benign nodules with test sensitivities of 89% and 83%. Lung cancer patients versus those with benign nodules were distinguished with 80% sensitivity. This study exhibits progress toward a minimally-invasive aid in early detection of lung cancer and monitoring small pulmonary nodules for malignancy.

Compatibility of ceftaroline fosamil for injection with selected drugs during simulated Y-site administration.

PURPOSE The physical compatibility of ceftaroline fosamil with commonly used medications and diluents (a total of 73 drugs in 219 admixtures) during simulated Y-site administration was evaluated. METHODS Duplicate 5-mL samples of ceftaroline fosamil (2.22 mg/mL) in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringers injection were combined at a 1:1 ratio with samples of 73 drugs (diluted or undiluted). Visual examinations were performed with the unaided eye in fluorescent light and with the aid of a Tyndall beam; the turbidity and particulate content of each sample were also measured. The compatibility of ceftaroline fosamil with propofol was evaluated by visually inspecting for emulsion separation and particle formation after centrifugation. All evaluations were performed within 15 minutes of sample preparation and at one and four hours after preparation. RESULTS Ceftaroline fosamil was physically compatible with 64 drugs in a combination of 196 admixtures for at least four hours, exhibiting color, clarity, turbidity, and microparticle content similar to those of control solutions. Signs of physical incompatibility, including visible precipitation, increased turbidity, and microparticle formation, were observed with 9 drugs in 23 admixtures during the four-hour observation period. CONCLUSION Of the 73 drugs evaluated, 64 were compatible and 7 were incompatible with ceftaroline fosamil 2.22 mg/mL in 3 standard infusion solutions. Nine drugs in 23 admixtures were observed to exhibit signs of incompatibility with ceftaroline fosamil within four hours of mixing; those drugs should not be simultaneously administered via a Y-site with ceftaroline preparations.