Interference of Parenteral Nutrition Components in Silicon-Mediated Protection Against Aluminum Bioaccumulation.

Aluminum and silicon are contaminants found in formulations used to prepare parenteral nutrition. Both elements are leached from glass containers, mainly during the heating cycle for sterilization. Insoluble and biologically inactive species of hydroxyaluminosilicates have been shown to form in solutions containing Al and Si. Therefore, this interaction may play an important role in protecting the body against Al toxicity. In this study, the bioavailability of Al in the presence of Si, calcium gluconate (Gluc.), and potassium phosphate (Phosf.) was investigated in rats. The rats were divided into 10 groups of 5 animals each: control, Al, Si, Al + Si, Gluc, Gluc + Al, Gluc + Al + Si, Phosf, Phosf + Al, and Phosf + Al + Si. The doses, consisting of 0.5 mg/kg/day Al and 2 mg/kg/day Si in the presence or absence of Gluc. or Phosf., were intraperitoneally administered for 3 months. Tissues were analyzed for Al and Si content. Al accumulated in the liver, kidneys, and bones, and the simultaneous administration of Si decreased Al accumulation in these tissues. The presence of Si reduced the amount of Al present by 72% in the liver, by 45% in the kidneys, and by 16% in bone. This effect was lees pronounced in the presence of parenteral nutrition compounds though. Si tissue accumulation was also observed, mainly when administered together with phosphate. These results suggest that Si may act as a protector against Al toxicity, by either reducing Al absorption or increasing its excretion, probably through hydroxyaluminosilicates formation. The presence of calcium gluconate and potassium phosphate decreases or inhibits this effect.

Simultaneous determination of iron and nickel as contaminants in multimineral and multivitamin supplements by solid sampling HR-CS GF AAS.

A methodology to assay simultaneously iron and nickel present as contaminants in multimineral and multivitamin supplements was investigated. High-resolution continuum source graphite furnace atomic absorption spectrometry and direct solid sample analysis were used. Measurements were done with the secondary lines of Fe (352.604 nm) and Ni (352.454 nm) to avoid spectral interferences. The best temperatures for pyrolysis and atomization for Fe and Ni were 1000 and 2700 °C, respectively. Chemical modifiers were not necessary and no matrix effects were observed. Aqueous standard solutions were used for calibration. The limit of detection was 0.517 µg g-1 for Fe and 0.011 µg g-1 for Ni. The precision ranged from 4.3% to 17% and 4.4-20% for Fe and Ni, respectively. The method accuracy was confirmed by comparing statistically the results obtained by solid sampling with those of sample acid digestion. The proposed methodology was successfully applied to determine both metals in different multimineral and multivitamin supplements.

Extraction/Leaching of Metal-Containing Additives from Polyvinyl Chloride, Ethyl Vinyl Acetate, and Polypropylene Bags and Infusion Sets into Infusion Solutions.

Flexible medical devices are primarily made of plasticized polyvinyl chloride (PVC). In recent times, to avoid undesired migration of the PVC plasticizers, ethyl vinyl acetate (EVA) and polypropylene (PP) has replaced PVC. Nevertheless, other additives are necessary to generate useful polymeric materials. Metallic species present in such additives can also leach out into the infusion solutions. The migration of barium (Ba), cadmium (Cd), lead (Pb), tin (Sn), and zinc (Zn) from devices made from PVC, EVA, and PP was evaluated. Bags and infusion sets were decomposed and their metallic contents analyzed. Glucose, NaCl, and Tween 80 were assessed as extraction media. These solutions were stored in PVC, EVA, and PP bags, heat-sterilized, and stored for 8 months at room temperature. Aliquots were taken before and after sterilization and then once per month to determine the contents of the metals. Commercial glucose and NaCl infusions were analyzed by taking aliquots of the solutions from the bags and from the administration set after their administration to patients. The three polymers contained the five metals. Ba was found in the highest concentration in all samples, with a mean of 8.0 mg/kg in PVC, 4.2 mg/kg in EVA, and 4.7 mg/kg in PP samples. Despite this, the only element that migrated into the glucose, NaCl, and Tween 80 solutions was Zn. The same result was found for the commercial glucose and NaCl infusions. Moreover, the Zn concentration in the administration sets was on average 52% higher than that found in the bags.LAY ABSTRACT: Flexible medical devices for infusions and artificial nutrition are made of plastics, such as polyvinyl chloride (PVC), ethyl vinyl acetate (EVA), and polypropylene (PP). These polymers contain additives necessary to generate useful materials. Metallic species present in these additives can leach out into the infusion solutions and come into contact with patients. To assess the risk of patient exposure to these metals, we evaluated the migration behavior of barium (Ba), cadmium (Cd), lead (Pb), tin (Sn), and zinc (Zn) from devices made from PVC, EVA, and PP. Bags and infusion sets were analyzed. Glucose, NaCl, and Tween 80 were investigated as extraction media. The three polymers contained the five metals. Ba was found in the highest concentration in all samples. Despite this, the only element that migrated into the glucose, NaCl, and Tween 80 solutions was Zn.

Determination of Antimony in Pharmaceutical Formulations and Beverages Using High-Resolution Continuum-Source Graphite Furnace Atomic Absorption Spectrometry.

A sensitive and accurate method, employing high-resolution continuum source atomic absorption spectrometry, for the determination of antimony (Sb) was developed. Conditions such as pyrolysis and atomization temperatures, the use of chemical modifiers, and sample pretreatment were optimized for the determination of Sb in pharmaceutical preparations and beverages stored in polyethylene terephthalate (PET) containers. In addition to container analysis, the influence of time of contact, temperature, and content composition on the migration of Sb was investigated. Twenty-six samples were periodically analyzed until finalize 1 year bottling. Eight mineral water samples were analyzed after storage at temperatures from 40 to 80°C for 48 h. Five different-colored PET samples were stored at 80°C for 20 days and periodically analyzed. Bottles, containing from 46.4 mg/kg Sb (amber PET) to 91.6 mg/kg Sb (colorless PET), leached Sb depending on the content ingredients, time of contact, and temperature. Although drinking water itself did not promote Sb migration at room temperature, juices and medicines did. After 1 year of storage, the Sb level in the samples ranged from 5 to 50 µg/L. The rate of leaching depended on the temperature, which was slow below 60°C, but rapidly increased at 60-80°C. The higher the Sb content in the bottle, the higher the amount of migration. Because Sb is a possible carcinogen to humans, containers for pharmaceutical use should be better controlled, and factors that increase Sb leaching in products that are widely consumed should be avoided.

Determination of chlorine via the CaCl molecule by high-resolution continuum source graphite furnace molecular absorption spectrometry and direct solid sample analysis.

This work investigates the possibilities of high-resolution continuum source graphite furnace molecular absorption spectrometry for the direct determination of Cl in solid samples via the CaCl molecule and measurement of its molecular absorption. The method proposed is based on addition of 400µg Ca as molecule-forming reagent and of 20µgPd as chemical modifier, which helps to stabilize the analyte and enhances sensitivity. The molecular spectrum for CaCl offers different lines with different limits of detection and linear ranges, which permitted to analyze solid samples with different Cl contents. The lowest limit of detection (0.75ng Cl, corresponding to 0.75µgg-1 for a typical sample mass of 1mg) could be achieved by combination of three of the most sensitive lines in the vicinity of 620.862nm, while the amplest linear range (up to 860ng Cl) was achieved by selection of the less sensitive line at 377.501nm. The method developed enabled the direct determination of Cl in solid samples using simple external calibration with aqueous standards. Good precision (5-9% RSD) and accuracy was attained in a series of certified samples of very different nature (i.e. coal, iron oxide, polyethylene, human hair, pine needles, rice flour and milk) and with very different Cl contents, ranging from about 50µgg-1 to 1% (w/w) Cl. The method appears as particularly useful for Cl determination in samples with elevated Ca contents, for which biased results with other diatomic molecules, such as AlCl or SrCl, may be obtained.

Applications of computational chemistry to the study of the antiradical activity of carotenoids: A review.

A summary of the various quantum chemical analyses that have been employed to evaluate the free radical scavenger capacity of carotenoid molecules are tabulated in this review and the most important observations are discussed. These molecules are able to interact with reactive oxygen species through singlet oxygen scavenging, electron transfer, hydrogen atom abstraction and radical adduct formation. Most studies employ density functional theory to compare the antiradical capacity of different carotenoids with the ones that are most explored theoretically, such as lycopene and ß-carotene. A significant number of these applications have been directed towards understanding the electron transfer mechanism, and a useful tool called the FEDAM (full-electron donor-acceptor map) was developed to better evaluate this mechanism. Important aspects that may affect the radical scavenging capacity of carotenoids, such as synergistic effects and solubility, are sometimes overlooked, and a greater number of such compounds should be explored.

Salting-out assisted liquid-liquid extraction and partial least squares regression to assay low molecular weight polycyclic aromatic hydrocarbons leached from soils and sediments.

A novel method was developed to determine low molecular weight polycyclic aromatic hydrocarbons in aqueous leachates from soils and sediments using a salting-out assisted liquid-liquid extraction, synchronous fluorescence spectrometry and a multivariate calibration technique. Several experimental parameters were controlled and the optimum conditions were: sodium carbonate as the salting-out agent at concentration of 2molL-1, 3mL of acetonitrile as extraction solvent, 6mL of aqueous leachate, vortexing for 5min and centrifuging at 4000rpm for 5min. The partial least squares calibration was optimized to the lowest values of root mean squared error and five latent variables were chosen for each of the targeted compounds. The regression coefficients for the true versus predicted concentrations were higher than 0.99. Figures of merit for the multivariate method were calculated, namely sensitivity, multivariate detection limit and multivariate quantification limit. The selectivity was also evaluated and other polycyclic aromatic hydrocarbons did not interfere in the analysis. Likewise, high performance liquid chromatography was used as a comparative methodology, and the regression analysis between the methods showed no statistical difference (t-test). The proposed methodology was applied to soils and sediments of a Brazilian river and the recoveries ranged from 74.3% to 105.8%. Overall, the proposed methodology was suitable for the targeted compounds, showing that the extraction method can be applied to spectrofluorometric analysis and that the multivariate calibration is also suitable for these compounds in leachates from real samples.

Simultaneous determination of cobalt and nickel in vitamin B12 samples using high-resolution continuum source atomic absorption spectrometry.

Nickel and cobalt were simultaneously assayed in vitamin B12 formulations by using atomic spectrometry. The proposed method is based on a compromise between the proximity of specific Ni and Co spectral lines and the relative abundances of the analytes in the samples. The analytes were found in concentrations ranging from 9.48 to 26.20µg L(-1) (Ni) and from 156.90 to 279.25mg L(-1) (Co) in the commercial samples of vitamin B12. The limits of detection and quantification were 1.21 and 3.64mg L(-1) for Co and 0.39 and 1.19µg L(-1) for Ni. Sample cleanup was not necessary for the determinations, and the interferences were discussed.

Ultrasound-Assisted Extraction and Biological Activities of Extracts of Brassica oleracea var. capitata.

In this work, the antioxidant and antimicrobial activities of Brassica oleracea var. capitata extracts obtained through ultrasound-assisted extraction are evaluated. The extracts obtained using the best extraction conditions were subjected to different hydrolysis conditions before their use in the biological tests. The crude and hydrolysed extracts were characterized using gas chromatography coupled with a mass detector. The use of ultrasound at 30 °C with 60% (by volume) solvent enabled obtaining a richer extract. All extracts had antioxidant activities against DPPH (13.0-80.0%), superoxide (35.2-63.2%) and peroxyl (89.3-99.5%) radicals, but the use of hydrolysed extracts considerably improved the antioxidant activities. Antimicrobial activities only of the hydrolysed extracts of Brassica oleracea var. capitata were detected. It was confirmed that antioxidant activity of vegetable extracts can be considerably increased when hydrolysis is applied as a pretreatment to their extraction.

Supercritical CO2 extraction, chemical characterisation and antioxidant potential of Brassica oleracea var capitata against HO·, O2(·-) and ROO·.

In this work were extracted bioactive compounds from Brassica oleracea var capitata using supercritical CO2 and evaluated the antioxidant potential of the extracts. Five extractions were accomplished to investigate the influence of pressure (10-25 MPa) and temperature (20-60 °C) in the extraction yield, chemical composition and antioxidant potential towards peroxyl, superoxide and hydroxyl radicals. The highest extraction yield was obtained at 60 °C and 25 MPa, which was 0.47 wt% (run 2). In the characterisation of the extracts obtained was possible the identification of sulforaphane and iberin nitrile that present known biological properties. The extracts of all runs presented antioxidant activities towards the three radicals, but the highest activities for all radicals were using the extracts obtained in the run 2. The use of supercritical CO2 extraction to obtain bioactive compounds of B. oleracea var capitata showed to be a promising alternative to conventional extraction methods, since allowed the extraction of compounds with scientific and industrial interest.

Aluminum content in intravenous solutions for administration to neonates: role of product preparation and administration methods.

BACKGROUND: Aluminum loading can reach toxic levels depending on the amount of aluminum intake in intravenous solutions (IV). Premature infants are at a higher risk of aluminum toxicity because of their reduced urinary aluminum elimination. All steps involved in the preparation of intravenous solutions for premature neonates in intensive care units were evaluated to determine to what degree, if any, they increased the aluminum load and should be considered when assessing the daily aluminum intake (<5 mcg/kg) established by the U.S. Food and Drug Administration (FDA). METHODS: Products and medical devices used for the IV administration of solutions to preterm neonates were analyzed for their aluminum content. Commercial formulations, bags after compounding, and medications before and after their preparation, as well as infusion sets (including burettes) and syringes, were evaluated for their contribution to the aluminum levels in the final solution. The determination was carried out by atomic absorption spectrometry. RESULTS: Currently available products used to prepare parenteral nutrition solutions as well as injectable medications usually administered to premature neonates present aluminum contamination. Bags, burettes, and syringes were also contaminated by aluminum to some degree, which may be leached during use. CONCLUSIONS: Commercial products are the main source of aluminum in parenteral nutrition; nevertheless, manipulation, containers, and administration sets increased aluminum levels by about 40%. Because this is a significant rate, these sources should be taken into account when calculating the amount of aluminum delivered to the patient in order to comply with FDA standards.

Low availability of aluminum in formulations for parenteral nutrition containing silicate.

BACKGROUND: Silicate (Si) and aluminum (Al) may be concomitant impurities in solutions for parenteral nutrition (PN). Silicate can bind to Al to form stable hydroxyaluminosilicates (HAS), thus reducing Al availability. This possibility is investigated by heating solutions containing constituents of PN in glass containers to promote the release of Si and Al. METHODS: The total amount of Si and Al in solution is measured by atomic absorption spectrometry, and the Al not bound to Si is evaluated by reaction with morin. RESULTS: When the Si:Al molar ratio is >5, no free Al is found in solution. For ratios <5, it is found that the lower the ratio, the higher the free Al fraction. However, in solutions of some amino acids, even with a low Si:Al ratio (<2), the amount of free Al is lower than that found in other solutions. The same tendency is observed among commercial formulations. Although in salt solutions the free fraction of Al reaches almost 100% when the Si concentration is low, in amino acid formulations the free fraction of Al does not surpass 50%. Moreover, even for Si:Al ratios >5, there is a "residual" fraction of free Al in amino acid formulations. CONCLUSIONS: The concomitant presence of Al and Si in solutions for PN reduces the amount of Al available attributable to the formation of HAS. In amino acid formulations this effect may be slightly reduced given the affinity of certain amino acids for Al. Therefore, amino acids may behave in the same fashion as silicate.

Performance of polymeric materials for solid phase extraction prior to chromatographic analysis.

Synthetic polymeric materials such as polyethylene and polyurethane (PU) were compared to conventional adsorbents for solid phase extraction for cleaning up biological samples. Efficiency in eliminating proteins and other components usually present in biological samples, such as serum, urine, and tissues extracts, was evaluated. The assays consisted of measuring the remaining protein content in serum and tissue homogenates (liver) and collecting the spectra in the UV region for urine samples. Since the analysis of many endogenous and exogenous species in these matrices usually involves chromatographic separation, the efficiency of the clean-up procedures was also evaluated by injecting cleaned samples into a C-18 chromatographic column with UV detection. Among the investigated polymers, polytetrafluorethylene, high density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMWPE) presented the best performance in retaining serum proteins. Proteic components of the liver homogenate were completely retained on polyurethane and polybutadiene (PB). Urine samples were cleaned by crossing columns of polytetrafluorethylene, ultra-high molecular weight polyethylene, high density polyethylene, polyurethane, and polyethylene co-butyl acrylate co-anhydride maleic (PEco), since the spectra collected after column percolation presented no peaks in the region between 190 and 390 nm. SPE cartridges showed different behavior, but along the lines of their usual performance; neither serum proteins nor urine components were retained on the phases and the liver components, though partially retained, were not desorbed with either water or methanol washes, with the exception of SAX. Chromatograms of samples cleaned with high density polyethylene showed that polymeric materials can be satisfactorily used as adsorbent for biological matrix components.

Tissue digestion for aluminum determination in experimental animal studies.

Four different procedures for the determination of aluminum in tissues by atomic absorption spectrometry (AAS) were investigated. They consisted of conventional acid digestion carried out before and after sample drying, associated or not with fat extraction. Drying was carried out in a conventional oven at 65 degrees C for 24 h. For fat extraction, different solvents and solvent mixtures were investigated considering both extraction yield and sample adequacy for further AAS measurement. Acid digestion was carried out with pure HNO3 or with its mixture with HClO4. After digestion, aluminum was measured by graphite furnace atomic absorption spectrometry. Tissues were collected from Al-exposed and nonexposed mice. The results indicated that drying the sample prior to digestion is advantageous as the amount of acid necessary can be significantly reduced. This procedure does not contribute to increase the aluminum level in the samples providing that careful measures to avoid contamination are taken, as the same procedures carried out without taking any precautions to avoid contamination produced imprecise results. Finally, aluminum was not found in the fatty fraction of any sample, even in exposed mice, demonstrating that aluminum does not accumulate in this part of the tissues.

Arsenic species in solutions for parenteral nutrition.

BACKGROUND: In spite of its high toxicity, arsenic is a common contaminant in pharmaceuticals. This is stated by pharmacopoeias' monographs where it is not generically included with other heavy metals, but has its own specifications. Arsenic should not exceed 0.1 mg/L in most pharmaceutical products for IV administration. This limit, however, was established without taking into consideration the specific arsenic species which contribute to this amount. In this work, the presence of arsenite and arsenate species in solutions of amino acids, salts, vitamins, and lipids commercialized for IV administration was investigated. METHODS: The measurements were done by hydride generation atomic absorption spectrometry. RESULTS: The results showed that all commercial formulations contain both arsenic species in some level; however, the total arsenic content exceeded the allowed limit in only a few samples. Calcium gluconate, sodium bicarbonate, heparin, and vitamin solutions were the most contaminated, presenting total arsenic concentration ranging from 62 to 249 microg/L. The most important finding, however, was the different ratios As(V)/As(III) among the formulations. Whereas practically only As(V) was found in ampoules containing water for injection and salt solutions (NaCl, KC1, phosphates), As(III) predominated in solutions of vitamins, gluconate, and glucose. As these are reducing substances, we investigated the possibility of their reaction with As(V) and its conversion into As(III). The heating of As(V) in the presence of gluconate, glucose, ascorbic acid, methionine, isoleucine, sodium chloride, and pure water, in autoclave for 15 minutes, showed that, whereas no As(III) was found in pure water and sodium chloride solution, approximately 50% of As(V) was converted into As(III) in the remainder of the solutions. CONCLUSIONS: The results showed that As(V), the main species in these formulations, may be converted into As(III), depending on the presence of reducing substances among the formulation constituents.

Determination of cadmium, lead and thallium in highly saline hemodialysis solutions by potentiometric stripping analysis (PSA).

Potentiometric stripping analysis (PSA) was investigated to assay simultaneously cadmium, lead and thallium present as contaminants in highly saline solutions used in hemodialysis. The saline matrices were sodium, potassium, magnesium and calcium chlorides, sodium acetate, sodium bicarbonate and glucose, which constitute concentrates for hemodialysis. A 1000mugmL(-1) Hg(II) solution was used to prepare the mercury film electrode (MFE) and to carry out the stripping step. After a 30s accumulation interval the analytes were simultaneously detected in the saline matrices without using masking agents. Determination limits of 80ngL(-1) for cadmium and thallium, and 50ngL(-1) for lead were calculated and a R.S.D. ranging from 0.5 to 2.2% (n = 3) was obtained measuring the analytes directly in commercial hemodialysis saline solutions. Recoveries from spiked samples ranging from 94.6 to 102.0% were obtained. The investigated metals were found in concentrations ranging from 2.7 to 5.7mugL(-1) for cadmium, 27.7 to 75.8muL(-1) for lead and 9.6 to 18.7mugL(-1) for thallium in commercial hemodialysis solutions. The PSA method showed to be adequate to the quality control of saline concentrates for hemodialysis.

Comparison of ultrafiltration and solid phase extraction for the separation of free and protein-bound serum copper for the Wilson's disease diagnosis.

BACKGROUND: The determination of the ratio free/protein-bound serum copper along with urinary copper can be used as a preliminary test for the Wilson's Disease diagnosis. In this work, the determination of these copper fractions in serum samples was carried out in two different ways; after separation of the copper bound to proteins from the free fraction by a column for protein adsorption and by ultrafiltration. As proteins can be adsorbed onto plastic polymeric surfaces, polyethylene (PE) with different molecular weights in powder form was investigated for protein adsorption. A small column was adapted in a flow system to carry out a solid-phase extraction (SPE) on-line. Preliminary experiments defined conditions for protein retention and elution and column saturation. Good performance was achieved using Mg(NO3)2 solution as carrier and methanol as eluent. The presence of proteins in both fraction (column effluent and eluate) was checked by the Coomassie Brilliant Blue test. Copper was measured by graphite furnace atomic absorption spectrometry. The measurement in the column effluent furnished the free-fraction of copper while the copper measured in the eluate the bound-fraction. The method was compared with ultrafiltration (20 kDa), measuring the free-copper in the ultrafiltrate. For the determination of protein-bound copper, the copper found in the ultrafitrate was discounted from the total copper measured in the sample. RESULTS: Serum samples of 10 individuals were analyzed by both methods with good agreement of the results. The regression plots, obtained by analysing the samples by both methods, presented r2 and slope of 0.97 and 0.96 for free copper and 1.00 and 1.00 for bound copper, respectively. Protein-bound copper (PB) concentrations ranged from 74 to 2074 microg/l and free-copper (F) from 22 to 54 microg/l. The ratio F/PB, calculated from SPE data, was 29.7% for one individual, with Wilson Disease well-characterized, and ranged from 1.2% to 5.2% for the others. CONCLUSION: The SPE method performed well in terms of accuracy and precision, and showed good agreement with the UF. Advantages of SPE are small sample volume (50 microl), separation carried out in 10 min, and the use of the same column for several analyses.

Critical evaluation of the standard hydrolytic resistance test for glasses used for containers for blood and parenteral formulations.

As prescribed by pharmacopoeias, containers should meet certain condition of stability to be used for pharmaceutical products. Glass containers are classified according to their resistance to chemical attack, a test executed by heating the glass in contact with water for 30 min at 121 degrees C. The USP powdered glass test for glass containers was applied to different kinds of glasses used as containers for parenteral formulations. In this experiment not only the released alkalinity was measured but also the release of glass constituents: silicate, borate, sodium, and aluminum, and also the release of some impurities as copper and lead. The USP powdered glass test was also carried out with glass ampoules, clear and amber, in the presence of solution of some inorganic salts, NaCl, KCl, CaCl2, MgCl2, NaHCO3, NaH2PO4, KH2PO4, and sodium gluconate, citric acid and glucose. The results showed that even when releasing very low alkalinity, glasses also released their constituents, in concentration ranges from 8.8 to 33 mg/l for silicate, 0.9 to 6.9 mg/l for borate, 3 to 37 for mg/l for sodium and 0.5 to 2.4 mg/l for aluminum. More expressive results were found, however, for the tests done with solutions instead of pure water. The tests showed that, for most of the solutions, while the measured alkalinity was very low, high levels of the other constituents were found. Basic solutions of bicarbonate and gluconate presented the higher levels of all investigated constituents, confirming the ability of basic solutions to attack and dissolve the glass network. Glucose and citric acid interacted with the glass surface, selectively extracting aluminum, copper, and lead. Whereas silicate, borate and sodium found in these solutions were at levels similar to those found with pure water, the aluminum level was almost 20 times higher. This specific action of citrate and glucose could be related to their metal-complexing ability. The results indicate that even so-called "chemical-resistant glasses," as measured by the hydrolytic resistance test, react with many substances when packaged in contact with them. The hydrolytic resistance test, when used as the sole measure of potential drug-container compatibility, is not reliable.

Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part III: Interaction container-chemicals during the heating for sterilisation.

The interaction of chemicals with the container materials during heating for sterilisation was investigated, storing the components of parenteral nutrition solutions individually in sealed glass ampoules and in contact with a rubber stopper, and heating the system at 121 degrees C for 30 min. Subsequently, the aluminium content of the solutions was measured by atomic absorption spectrometry (AAS). The assay was also carried out with acids, alkalis and some complexing agents for Al. The containers were decomposed and also assayed for aluminium. 30 different commercial solutions for parenteral nutrition, stored either in glass or in plastic containers, were assayed measuring the aluminium present in the solutions and in the container materials. The results of all investigated container materials revealed an aluminium content of 1.57% Al in glass, 0.05% in plastic and 4.54% in rubber. The sterilisation procedure showed that even pure water was able to extract Al from glass and rubber, 22.5 +/- 13.3 microg/L and 79.4 +/- 22.7 microg/L respectively, while from plastic the aluminium leached was insignificant. The Al released from glass ampoules laid between 20 microg/L for leucine, ornithine and lysine solutions and 1500 microg/L for solutions of basic phosphates and bicarbonate; from rubber stoppers it reached levels over 500 microg/L for cysteine, aspartic acid, glutamic acid and cystine solutions. Ion-exchange properties and influence of pH can explain the interaction of glass with some chemicals (salts, acids and alkalis), but only an affinity for aluminium could explain the action of some amino acids and other chemicals, as albumin and heparin, on glass and rubber, considering the aluminium release. Experiments with complexing agents for Al allowed to conclude that the higher the stability constant of the complex, the higher the Al release from the container material.

Contribution of the raw material to the aluminum contamination in parenterals.

BACKGROUND: The extent of aluminum contamination in parenteral nutrition solutions was measured in 35 different commercial products, including amino acids, electrolytes, glucose, lipids, vitamins trace elements, and albumin. The extent of aluminum contamination in substances used as raw material for preparation of parenterals was also measured. Chemicals from different manufacturers and of different quality grades were analyzed individually. METHODS: The measurements were done by atomic absorption spectrometry. RESULTS: The results showed that the same product might have different aluminum content depending on the manufacturer, either for commercial formulations or substances. The highest contaminated chemicals included cystine, NaOH, vitamin C, biotin, gluconate, and Fe and Cr salts. The lowest contaminated chemicals included lipids, apolar amino acids, glucose, HCI, acetic acid, KCl, NaCl, and heparin. Among commercial products, the major contamination rates appeared in calcium gluconate, followed by trace elements, some vitamins, bicarbonate, phosphates salts, and heparin. CONCLUSIONS: Comparing the aluminum in commercial products and substances, it can be concluded that the contamination may occur in parenterals because aluminum is present naturally in the chemicals. However, when the composition and concentration of the parenteral solution are considered, the contamination of calcium gluconate, trace elements, some vitamins, phosphates, bicarbonate, and heparin cannot be related only to the raw substances. The aluminum level present in these commercial formulations is too high to come only from the substances; therefore, it is possible that one of the steps of the manufacturing procedure is responsible for elevating the contamination of these products.