Short-term Stability Test Research Articles

Homogeneity and stability study of the candidate reference material Adamussium colbecki for trace elements

The preparation of a new candidate certified reference material (CRM) for trace elements based on the antarctic bivalve Adamussium colbecki(IRMM 813) was carried out by the Istituto Superiore di Sanità(ISS, Rome, Italy) in cooperation with the Institute for Reference Materials and Measurements, Joint Research Centre of the European Commission (EC-JRC-IRMM), in the frame of the Italian National Programme of Research in Antarctica (Programma Nazionale di Ricerca in Antartide, PNRA). Samples were collected at Terra Nova Bay (Ross Sea) during the 2000-2001 expedition in Antarctica. The preparation of a material suitable for certification was performed by the EC-JRC-IRMM. Measurements for homogeneity and short-term stability tests were carried out by ISS. The elements selected for the certification project were As, Cd, Cu, Cr, Fe, Mn, Ni and Zn. For the above-mentioned tests, the determination of the elements of interest was performed on samples mineralised by microwave-assisted acid digestion. The analytical techniques employed to this end were inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma dynamic reaction cell quadrupole mass spectrometry (ICP-DRC-Q-MS). The candidate material was shown to be fit for purpose with regard to homogeneity and short-term stability, thus allowing the following phases of the certification project to be undertaken, in the first place the selection of expert laboratories for the accomplishment of the certification campaign.

Protocols for stability and homogeneity studies of drugs for its application to doping control

Practical procedures for testing the homogeneity and the stability of drugs in biological fluids, with especial attention to antidoping control, and criteria for data evaluation are proposed. The stability of the analytes was evaluated at −20 and 4 °C in liquid urine and at 4 °C in freeze-dried urine for up to 24 months. A stock of samples was stored at low temperatures (−80 °C) for comparison purposes. Higher temperatures (e.g. −40 or −20 °C) can be used as reference provided that the analyte has proved to be stable under these conditions. For short-term stability testing, aliquots of the urine sample were analyzed after 3 and 7 days of storage at 37 °C. Stability of the analytes after going through three freeze and thaw cycles was also determined. According to the results obtained, long-term stability studies are recommended to be performed by using a sample stored at a reference condition that has to be analyzed at the same time as the test conditions samples. The use of a reference aliquot analyzed in parallel has the potential of allowing the performance of stability studies by using qualitative methods. In these cases, the signal of the analyte is used in the calculations instead of concentration values. This approach has demonstrated to be useful to assess analyte stability independently of the analytical technique applied to analyze urine samples (high-performance liquid chromatography, gas chromatography with nitrogen–phosphorus detection or mass spectrometry detection). The use of qualitative methods can be also considered for homogeneity, and short-term and freeze–thaw stability studies, where the reference sample is also analyzed at the same time as the test samples. The criteria proposed for evaluating the stability and homogeneity are based on the precision of the analytical method. The suitability of the protocols and the criteria for data evaluation has been demonstrated by studying the stability of samples containing caffeine, ephedrine derivatives, amphetamine derivatives, and testosterone and epitestosterone glucuronides.

Protocols for stability and homogeneity studies of drugs for its application to doping control

Practical procedures for testing the homogeneity and the stability of drugs in biological fluids, with especial attention to antidoping control, and criteria for data evaluation are proposed. The stability of the analytes was evaluated at −20 and 4 °C in liquid urine and at 4 °C in freeze-dried urine for up to 24 months. A stock of samples was stored at low temperatures (−80 °C) for comparison purposes. Higher temperatures (e.g. −40 or −20 °C) can be used as reference provided that the analyte has proved to be stable under these conditions. For short-term stability testing, aliquots of the urine sample were analyzed after 3 and 7 days of storage at 37 °C. Stability of the analytes after going through three freeze and thaw cycles was also determined. According to the results obtained, long-term stability studies are recommended to be performed by using a sample stored at a reference condition that has to be analyzed at the same time as the test conditions samples. The use of a reference aliquot analyzed in parallel has the potential of allowing the performance of stability studies by using qualitative methods. In these cases, the signal of the analyte is used in the calculations instead of concentration values. This approach has demonstrated to be useful to assess analyte stability independently of the analytical technique applied to analyze urine samples (high-performance liquid chromatography, gas chromatography with nitrogen–phosphorus detection or mass spectrometry detection). The use of qualitative methods can be also considered for homogeneity, and short-term and freeze–thaw stability studies, where the reference sample is also analyzed at the same time as the test samples. The criteria proposed for evaluating the stability and homogeneity are based on the precision of the analytical method. The suitability of the protocols and the criteria for data evaluation has been demonstrated by studying the stability of samples containing caffeine, ephedrine derivatives, amphetamine derivatives, and testosterone and epitestosterone glucuronides.

Stability studies of selected doping agents in urine: caffeine

The stability of caffeine in urine samples has been studied. A high-performance liquid chromatography (HPLC) method for the quantification of caffeine in urine samples was validated for that purpose. The method consists of a liquid–liquid extraction at alkaline pH with chloroform-2-propanol (9:1, v/v) with a salting out effect. 7-Ethyltheophylline was used as internal standard (ISTD). Analyses were performed with an Ultrasphere ODS C18 column using water/acetonitrile (90:10, v/v) as a mobile phase at a flow rate of 1 ml/min. Ultraviolet absorption at 280 nm was monitored. Extraction recoveries for caffeine and 7-ethyltheophylline were 81.4±6.0 and 87.3±5.7%, respectively. The calibration curves were demonstrated to be linear in the working range of 6–30 μg/ml ( r 2>0.990). The limit of detection and the limit of quantitation were estimated as 0.7 and 2.0 μg/ml, respectively. Precisions in the range of 1.5–9.2 and 4.1–5.8% were obtained in intra- and inter-assay studies, respectively, using control samples containing 10, 14 and 26 μg/ml of caffeine. Accuracies ranging from 2.9 to 7.4% for intra-assay experiments, and from 3.9 to 5.4% in inter-assay studies were obtained. Stability of caffeine in urine samples was evaluated after long- and short-term storage at different temperature conditions. The batches of spiked urine were submitted to sterilization by filtration. No adsorption of the analyte on filters was observed. Before starting stability studies, batches of reference materials were tested for homogeneity. For long-term stability testing, caffeine concentration in freeze-dried urine stored at 4 °C and in liquid urine samples stored at 4, −20, −40 and −80 °C was determined at several time intervals for 18 months. For short-term stability testing, caffeine concentration was evaluated in liquid urine stored at 37 °C for 7 days. The effect of repeated freezing (at −20 °C) and thawing was also studied for up to three cycles. The stability of caffeine was also evaluated in non-sterile samples stored at −20 °C for 18 months. No significant loss of the compound was observed at any of the investigated conditions.

Performance of an air-breathing direct methanol fuel cell

Abstract An air-breathing direct methanol fuel cell (DMFC) is attractive for portable-power applications. There are, however, several barriers that must be overcome before DMFCs reach commercially viability. This study shows that the cell power density is strongly affected by the fabrication conditions of the membrane electrode assembly (MEA) and by the technique used for assembly of the cell components. The results indicate that reducing the pressure and the thickness of catalyst layer in the MEA fabrication process can significantly improve power density. The production of water at the cathode, especially at a high power density, is shown to have a strong impact on the operation of an air-breathing DMFC since water blocks the feeding of air to the cathode. The power density (≧20 mW cm −2 ) of an air-breathing DMFC is found to drop to nearly half of its initial value after 30–40 min of operation in a short-term stability test. This appears to be one of the major limitations for potable electronic applications. Despite the many practical difficulties associated with an air-breathing DMFC, an attempt is also made to highlight the importance of the component assembly technique using a small cell pack with four integrated unit cells.

Determination of the optimal amount of water in liquid-fill masses for hard gelatin capsules by means of texture analysis and experimental design

The aim of this study is to use texture analysis as a non-destructive test for hard gelatin capsules filled with liquid formulations to investigate mechanical changes upon storage. A suitable amount of water in the formulations is determined to obtain the best possible compatibility with the gelatin shell. This quantity of water to be added to a formulation is called the balanced amount of water (BAW). Texture profiling was conducted on capsules filled with hydrophilic polymer mixtures and with formulations based on amphiphilic masses with high HLB value. The first model mixture consisted of polyethylene glycol 400 and polyvinylpyrrolidone K17 with water and the second type consisted of caprylocaproyl macrogol glycerides (Labrasol®) with colloidal silica (Aerosil® 200) and water. The liquid-fill capsules were investigated by measuring changes on mass and stiffness after storage under confined conditions in aluminium foils. Capsule stiffness was investigated also as a parameter in a response surface analysis to identify the BAW. Polyvinylpyrrolidone did not show a great influence on the BAW in the range of 10–12% (w/w) for the first model mixture. Capsules with the less hydrophilic Labrasol® formulations, however, kept their initial stiffness after storage best with only half of that amount, i.e. 5–6% (w/w) of water in the compositions. From this study it can be concluded that texture profiling in the framework of an experimental design helps to find hydrophilic or amphiphilic formulations that are compatible with gelatin capsules. Short-term stability tests are meaningful if capsule embrittlement or softening is due to water equilibration or another migration process that takes place rapidly. Long-term stability tests will always be needed for a final statement of compatibility between a formulation and hard gelatin capsules.

Determination of five selenium compounds in urine by liquid chromatography with focused microwave assisted digestion and hydride generation–atomic absorption spectrometric detection

A method is proposed for the determination of trimethylselenonium ion, selenomethionine, selenocystine, selenite and selenate in urine, following clean-up with C 18 cartridges. The on-line system developed consists of an anion-exchange chromatographic column for species separation, a focused microwave oven for the oxidation of organic Se species in the presence of 3% K 2S 2O 8 and 3% NaOH solution and reduction of selenate to selenite in 10 mol l −1 HCl, a hydride generation system for the conversion of selenite to selenium hydride and finally an atomic absorption spectrometer detector. Optimum chromatographic conditions were obtained in a Hamilton PRP-X100 column, using 100 mmol l −1 phosphate buffer (pH=6.8) as the mobile phase. Detection limits were between 3 and 8 μg l −1. The relative standard deviation was <7% at 100 μg l −1 Se. The short-term stability test of the studied Se species in urine shows after 5 h of storage about 30% and 60% losses of selenite and SeCys, respectively. After taking pills containing Se about 60% of the Se ingested is excreted in the first 12 h. Se(VI) ingested is partially excreted as Se(VI) and partially transformed and excreted as a species that behaves as SeCys. SeMet is metabolised and excreted as species that behave as Se(VI) and SeCys.

Formulation and preparation of controlled release pellets of salbutamol by the air suspension technique

A controlled release preparation of salbutamol may improve patient compliance, minimise side effects and be valuable in the treatment of nocturnal asthma by extending drug action throughout the night. The aim of the study was therefore to formulate a controlled release pellet preparation of salbutamol via the air suspension technique. The study established that curing for 24 h at 38 ± 0.5°C was necessary for homogeneous film coats of Eudragit® RS30D and hence stable drug release characteristics. Pellets coated with 6% Eudragit® RS30D (polymer), 12.5% triethyl citrate (plasticiser) and 0.5% magnesium stearate (antitacki-ness agent) displayed desirable controlled drug release characteristics over the 8 h testing period. The manufacturing conditions employed in the study were shown to be reproducible thus ensuring reproducibility of drug release characteristics between batches of salbutamol controlled release pellets. Short term stability testing on the newly formulated pellets indicated no significant change in drug release characteristics relative to the initial drug release data when stored for 8 weeks at room temperature 20 ± 2°C or 37°C with 80% Relative Humidity or at low temperature (5 ± 1°C). However, pellets stored at 40°C showed a slower in-vitro drug release after 8 weeks of storage and therefore failed to maintain their initial drug release profile.

Heat-treated iron and cobalt tetraphenylporphyrins adsorbed on carbon black: Physical characterization and catalytic properties of these materials for the reduction of oxygen in polymer electrolyte fuel cells

Iron and cobalt tetraphenylporphyrins (FeTPP and CoTPP, respectively) have been adsorbed on carbon black (C). The resulting FeTPP/C and CoTPP/C were heat-treated in Ar at various temperatures ranging from 100–1100 °C in order to produce catalysts for the electroreduction of oxygen in polymer electrolyte fuel cells. The catalysts have been characterized by XRD, XPS, ToF-SIMS, and bulk analyses. Their electrocatalytic properties have been evaluated by rotating disk electrode ( rde) and gas diffusion electrode ( gde) measurements. The highest rde activities at 0.70 V vs nhe were recorded for CoTPP/C and FeTPP/C heat-treated in the 500–700 °C range. In that temperature range, the increased catalytic activity originates from the well dispersed N 4-metal moiety or from fragments of the original molecule still containing the metal bound to nitrogen. Short term stability tests on the initially most active catalysts revealed the instability of these catalysts in comparison to those obtained at higher pyrolysis temperatures (900–1000 °C). At these pyrolysis temperatures the active site of the catalysts is inorganic in nature. The presence of iron and cobalt in their metallic states in these catalysts has been confirmed using XRD. TEM of the catalysts pyrolyzed at these higher temperatures revealed that most of the iron and cobalt are encapsulated in a graphite-like coating. The better stability of these catalysts in the acidic environment of a working fuel cell may be ascribed to the presence of this protective coating. The activity of FeTPP/C pyrolyzed at 1000 °C was observed to increase with time in a manner similar to that of platinum-based catalysts. The activity of the former catalyst was determined to be approximately one half that of a commercial platinum catalyst containing the same amount of metal (2 wt%).

Evaluation of a Direct-Injection Nebulizer (DIN) for Liquid Sample Introduction in Helium Microwave-Induced Plasma Mass Spectrometry (MIP-MS)

A direct-injection nebulizer (DIN) has been evaluated for liquid sample introduction in helium microwave-induced plasma mass spectrometry (MIP-MS). A short-term stability test with the direct-injection nebulizer was found to give less than 0.5% RSD for twenty minutes. Isotope abundances for K, Ca, Cr, and Se were determined with less than 10% error on all isotopes. All elements have linear dynamic ranges of two to three orders of magnitude. Detection limits are low to sub-ppb for all elements. Ion lens tuning plays an important role in multielement determinations. Oxide, hydroxide, and doubly charged ions are determined for Cr, As, Sr, Cs, Ba, and Pb. The effect of 10% methanol and high-dissolved salts is investigated.

Thermospray nebulization as sample introduction for inductively coupled plasma mass spectrometry

A sample introduction system, consisting of a thermospray nebulizer and a desolvating unit, was coupled to an inductively coupled plasma mass spectrometer. Several parameters were optimized including the sample uptake rate, the power delivered to the capillary tube, the temperature of the aerosol and of the cooling-water, the carrier gas flow rate and the r.f. power. Under optimized conditions, the sensitivity obtained with the thermospray system is a factor of 10 higher than with a pneumatic nebulizer combined with a spray chamber. The increase was observed for the following elements over the whole mass range: Be, Al, Sc, Co, In, Gd, Tl, Th and U. Since similar background levels, 10–40 counts s–1, were observed, better detection limits could be achieved (from 0.19 ng l–1 for U to 1.3 ng l–1 for Be). The relative standard deviation (RSD) on analyte signals for a short-term stability test (10 min) is between 3 and 8%. These values can be improved to less than 4% by the use of internal standardization. No drift in analyte signal during several hours was observed. The levels of oxide (MO+:M+) and doubly charged (M2+:M+) ions obtained with the thermospray system are about a factor of 2.5 lower than those obtained with the pneumatic system. Consequently, the oxide ion levels for elements with the highest MO bond strength and the doubly charged ion levels for elements with the lowest second ionization energy are not above 1%.

Cd1-xZnxSe photo-anodes: I. Auger electron spectroscopy and scanning electron microscope studies

A preparatory technique for Cs1-xZnxSe films is described. The results of investigations on the composition, surface features and photocorrosion of the Zn-ion-treated CdSe films have also been reported. It is shown that the annealing of these films at 100 degrees C for 30 minutes causes diffusion of Zn deep within the bulk. The resulting Cd1-xZnxSe films have also been examined by a scanning electron microscope. It is shown that the Zn adsorption and diffusion is mediated mainly via the grain boundaries. Short-term stability tests indicate that the S to or from Se exchange as a result of photocorrosion in the sulphide/polysulphide electrolyte is considerably reduced in Cd1-xZnxSe films compared to the CdSe films.