Bacterial monitoring in vials using a spectrophotometric assimilation method.

Aseptic-filling processes are often used with fragile parenteral products that might be destroyed by terminal autoclaving. However, aseptic filling is not as effective as autoclaving in reducing contamination. As a result, time-consuming microbiological methods and turbidimetry are employed currently as product inspection techniques, but these processes can destroy the product and might not detect low levels of contamination. Thus, near-infrared (IR) light scattering was evaluated in this study as a new method for determining low levels of contamination noninvasively and nondestructively. A new parallel mathematical technique was used in conjunction with near-IR spectrophotometry to detect successfully contamination by several species of bacteria through intact glass vials. Using the near-IR method, products can be evaluated without introducing contamination, preserving the sample vial for dispensing or evaluation by another method.

Near-infrared spectrometry of microorganisms in liquid pharmaceuticals.

Biotechnology and pharmaceutical research have created a number of new and potentially life-saving drugs. Many of these drugs are formulated as injectable products. Some drug products do not survive autoclaving or other means of terminal sterilization. An aseptic filling process is typically used to sterilize such products, but it is less reliable than autoclaving, making detection of unsterile units even more essential. Invasive microbiological methods and turbidimetry are currently employed as inspection techniques. These processes are time-consuming, destroy product, and may not detect low levels of contamination. Near-IR light scattering is proposed as a new method of determining low levels of contamination noninvasively and nondestructively. The method is used successfully in the current study to detect contamination by a species of yeast, mold, and bacteria in intact plastic infusion bags at levels as low as three colony-forming units per milliliter for yeast. By use of the near-IR method, each injectable unit can be evaluated with its integrity maintained, allowing the product to be dispensed or evaluated by another analytical method.

Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature.

The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high-performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen.

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.

Determination of bepridil in biological fluids by high-performance liquid chromatography.

A rapid, selective and sensitive assay has been developed for the determination of the anti-anginal drug, bepridil, in biological samples. The lowest concentration of bepridil which can be measured accurately and precisely in a 2-ml plasma or urine sample is 10 ng/ml. The standard curve is linear in the concentration range 10-2000 ng/ml. Accuracy and precision of the assay, expressed as relative deviation and coefficient of variation (inter-run) are less than 6.5% at all concentrations in the linear range. No interfering peaks are observed. Using an automatic injector and a laboratory computer system, 48 samples are analyzed routinely in an 8-h day.