Physical Compatibility of Cefiderocol with Selected Intravenous Drugs During Simulated Y-site Administration.

The physical compatibility of cefiderocol for injection (prepared as a diluted 2% cefiderocol solution) with potential co-administration drug products is presented. The compatibility of cefiderocol with a selection of 91 intravenous drugs was tested at clinically relevant concentrations using the admixed volume ratio 1:1. Compatibility of the mixtures was determined by visual observations, turbidity, and particulate-matter measurements. The mixtures were examined immediately after mixing, and then at 1 hour and 4 hours thereafter at room temperature. When using 0.9% sodium chloride or 5% dextrose injection for diluents, solutions of dobutamine hydrochloride, esomeprazole sodium, methylprednisolone acetate, propofol, rocuronium bromide, amiodarone hydrochloride, famotidine, labetalol hydrochloride, mycophenolate mofetil, acyclovir sodium, amphotericin B, caspofungin acetate, doxycycline, posaconazole, diphenhydramine hydrochloride, and phenytoin sodium were found to cause visible cloudiness upon mixing with 2% cefiderocol in both diluents. Solutions of lorazepam, tobramycin sulfate, and vancomycin hydrochloride were determined incompatible by examining the mixtures with the aid of a Tyndall light. These 19 drugs were clearly incompatible with cefiderocol for injection by visual examination. In addition, solutions of iron sucrose and albumin were incompatible with 2% cefiderocol based on sub-visual tests for turbidity and/or particulate matter. Based on sub-visual data, the 0.9% sodium chloride admixture of aminophylline and 2% cefiderocol was incompatible, while inconclusive results were obtained for the 0.9% sodium chloride admixtures of 2% cefiderocol with amikacin sulfate. Similarly, the 5% dextrose admixtures of either ciprofloxacin or polymyxin B sulfate with 2% cefiderocol were incompatible, whereas data for phenylephrine hydrochloride morphine sulfate, or undiluted sodium bicarbonate were inconclusive. Overall, the 2% cefiderocol solution was physically compatible with 63 of 91 drugs challenged at 1:1 volume ratio in both 0.9% sodium chloride and 5% dextrose diluents for at least 4 hours at the concentrations tested in this study.

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

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.

Topical Metered-dosing Dispenser Performance Evaluation.

Topical metered-dosing dispensers are designed for dosing accuracy and ease-of-use by the patients while protecting the packaged products from environmental exposure and contamination. The objective of this study was to evaluate the accuracy, precision, and residual of available topical metered-dosing dispensers with different types of topical cream for practical application. Triplicate samples of five different dispensers were tested. This test was completed using three types of commercial topical cream-bases of dissimilar Total Active Pharmaceutical Ingredient Load Percentages, Transdermal Penetration Percentages, and Specific Gravities. The dispensers were evaluated according to specified dose-uniformity criteria for a total dispensing capacity of 30 mL at 0.5 mL per dose for 60 doses. The study shows Topi-CLICK performed with the best precision and accuracy of dosing in comparison to the airless-pump type dispensers. While the dispensing was highly variable with airless pumps and may require calibration for each packaged product, remarkably the performance of Topi-CLICK was not affected by different types of cream-bases and does not require additional metering calibration.

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.

Serum discrimination of early-stage lung cancer patients using electrospray-ionization mass spectrometry.

The goal of this study was to evaluate the usefulness of electrospray ionization-mass spectrometry (ESI-MS) technology to distinguish sera of early-stage lung cancer patients from control individuals. ESI-MS m/z (mass divided by charge) data were generated from sera of 43 non-small cell lung cancer patients (pathological stages I and II) and 21 control individuals. Identifications of m/z peak area significances between cancer and control ESI-MS sera spectra were performed using t-tests. A "leave one out" cross validation procedure, which mimics blinded sera analysis and corrects for "over-fitting" of data, yielded discriminatory cancer versus control distribution p value and ROC curve area value of <0.001 and 0.87, respectively. Analysis without the "leave one out" cross validation procedure yielded a ROC curve area of 0.99 for discrimination of sera from lung cancer patients versus control individuals. Predictive value measurements revealed overall test efficiency and sensitivity for distinguishing sera from lung cancer patients from controls (using "leave one out" cross validation) of 80% and 84%, respectively. ESI-MS serum analysis between control individuals and lung cancer patients who smoked or did not smoke had p values in ranges indicating that smoking effects are not pronounced in our analysis. These studies indicate that ESI-MS analyses of sera from early stage non-small cell lung cancer patients were helpful in distinguishing these patients from control individuals.

Stability of Metronidazole Benzoate in SyrSpend SF One-Step Suspension System.

The objective of this study was to determine the stability of metronidazole benzoate suspension in SyrSpend SF One-Step Suspension system. The studied samples were packaged in 60-mL amber plastic prescription bottles, which were stored protected from light under controlled environmental conditions for a period of 360 days. Stability of metronidazole benzoate suspension in SyrSpend SF was assessed based on retention of initial color or appearance, pH of suspension, and recovery of metronidazole benzoate from the packaged product. Duplicate samples were evaluated at each predefined time interval. An assay method by high performance liquid chromatography was validated for its specificity and stability-indicating characteristscs through a forced-degradation study, and was used in metronidazole benzoate assay. Metronidazole benzoate in SyrSpend SF retained its normal appearance of an opaque suspension, with acceptable pH values ranging from 4.43 to 4.53 (range 4.45 +/- 0.5). Recovery of metronidazole benzoate at subsequent time points was within 90% to 110% of inital concentration for samples stored at refrigerated temperature (2 deg C to 8 deg C), and ambient condition (25 deg C/60% relative humidity), with no detectable changes in chromatographic profile for most tested samples. The rates of change in potency for metronidazole benzoate were determined under the assumptions of first-order kinetics, and the time to reach 90% to 110% initial concentration was determined to be 366 days for samples in ambient storage, or 716 days for samples stored at refrigerated temperature. Metronidazole benzoate in SyrSpend SF, which was packaged in amber plastic prescription bottles, is stable for at least 1 year when stored protected from light at ambient condition (25 deg C/60% relative humidity). The shelf life for this product may be extended to 2 years when stored at refrigerated temperature.

Ethanol formation in unadulterated postmortem tissues.

During the investigation of aviation accidents, postmortem samples obtained from fatal accident victims are submitted to the FAA's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Many species of bacteria, yeast, and fungi have the ability to produce ethanol and other volatile organic compounds in postmortem specimens. The potential for postmortem ethanol formation complicates the interpretation of ethanol-positive results from accident victims. Therefore, the prevention of ethanol formation at all steps following specimen collection is a priority. Sodium fluoride is the most commonly used preservative for postmortem specimens. Several studies have been published detailing the effectiveness of sodium fluoride for the prevention of ethanol formation in blood and urine specimens; however, our laboratory receives blood or urine in approximately 70% of cases. Thus, we frequently rely on tissue specimens for ethanol analysis. The postmortem tissue specimens received by our laboratory have generally been subjected to severe trauma and may have been exposed to numerous microbial species capable of ethanol production. With this in mind, we designed an experiment utilizing unadulterated tissue specimens obtained from aviation accident victims to determine the effectiveness of sodium fluoride at various storage temperatures for the prevention of microbial ethanol formation. We found that without preservative, specimens stored at 4 degrees C for 96 h showed an increase in ethanol concentration ranging from 22 to 75 mg/hg (average 42 +/- 15 mg/hg). At 25 degrees C, these same specimens showed an increase ranging from 19 to 84 mg/hg (average 45 +/- 22 mg/hg). With the addition of 1.00% sodium fluoride, there was no significant increase in ethanol concentration at either temperature.