Leachables analysis

As to the analysis of trace elements in paper, cardboard and raw materials for the production of paper, high concentration elements such as Cu, Fe or Ti can easily be determined by FAAS Cd and Pb are frequently analysed by GFAAS. Cadmium in pulp and paper was determined by AAS after pressurised digestion with nitric acid [145]. An interlaboratory comparison of Cd in wrapping paper was reported, mainly based on pressure digestion in FIFE bombs with sub-boiled nitric acid, followed by ETAAS [59]. For wrapping paper used for foodstuffs, next to the total content of toxic heavy metals, the soluble or leachable fraction is of particular interest. 

Example Optimization of an Eleven Component Glass Formulation. Piepel (6) discussed the generation and analysis of a mixture design consisting of eleven oxides used to prepare glasses for waste vitrification. Although many responses must be considered for the end use of this composition, the intent of Piepel s study was to minimize the response of leachability subject to the compositional constraints of ... 

Once the sample preparation is complete, there are several approaches to the analysis of petroleum constituents in the water and soil (1) leachability or toxicity of the sample, (2) the amounts of total petroleum hydrocarbons in the sample, (3) petroleum group analysis, and (4) fractional analysis of the sample. These methods measure different petroleum constituents that might be present in petroleum-contaminated environmental media. 

Two different approaches have been taken by researchers to determine the secondary mineralogy of CCBs (1) direct observation, which is accomplished via analysis of weathered ash materials, and (2) prediction, based on chemical equilibrium solubility calculations for ash pore-waters and/or experimental ash leachate or extractant solutions. Because the secondary phases are typically present in very low abundance, their characterization by direct analysis is difficult. On the other hand, predictions based on chemical equilibrium modelling or laboratory leaching experiments may not be reliable indicators of element leachability or accurately indicate the secondary phases that will form under field conditions (Eighmy et al. 1994 Janssen-Jurkovicova et al. 1994). 

Samples of the red clay having uniform physical and chemical characteristics were provided by G. R. Heath of the University of Rhode Island. The samples were obtained from core LLUU-GPC-2, collected on October 11, 1976, at 30° 20.9 n, 157° 50.85 w, water depth 5821 meters, and are representative of the smectite-rich region of the red clays which occurs in the sediment at depths below about ten meters. In this region, the sediment appears to contain about five to six percent by weight leachable iron and manganese in the form of hydrous oxides. The remaining material appears to be dominated by iron-rich smectite and lesser, varying amounts of phillipsite (2). The results of a semi-quantitative (precision in data is within a factor of 2) elemental analysis... 

Reverse osmosis for concentrating trace organic contaminants in aqueous systems by using cellulose acetate and Film Tec FT-30 commercial membrane systems was evaluated for the recovery of 19 trace organics representing 10 chemical classes. Mass balance analysis required determination of solute rejection, adsorption within the system, and leachates. The rejections with the cellulose acetate membrane ranged from a negative value to 97%, whereas the FT-30 membrane exhibited 46-99% rejection. Adsorption was a major problem some model solutes showed up to 70% losses. These losses can be minimized by the mode of operation in the field. Leachables were not a major problem. 

A routine screening test first involved a series of flush-discard cycles followed by a period (3-4 h) of total recycle with nonspiked synthetic tap water. Analysis of water at the end of the recirculation period provided an assessment of flush efficiencies and an estimate of leachable organic substances. 

The results showed that there was no increase in leachate metals concentration after ten extractions. Most of the metal concentrations remained the same or decreased during the total MEP run. This proves the long term stability of the CHEMFIX product since the MEP was designed to simulate conditions of 1000 years of acid rain exposure. In addition, throughout the entire MEP analysis the leachable metals concentrations were all below the regulatory limits. Thus once the soil is treated by the CHEMFIX process it remains non-hazardous for extended periods of time. 

Gong, Z., Lu, X., Watt, C. et al. (2006) Speciation analysis of arsenic in groundwater from Inner Mongolia with an emphasis on acid-leachable particulate arsenic. Analytica Chimica Acta, 555(1), 181-87. 

As a result, materials for medical devices and drug products must be tested for leachable components. Once a known toxic compound is discovered, it must be identified for the assessment of toxicity, followed by the monitoring of levels using validated methods as required by the FDA. This identification procedure could be a time-consuming process with traditional methods that are based on fractionation and individual component analysis. 

Figure 6.44 Chromatograms from the LC/UV/ion trap MS analysis of leachables that were extracted from a test adhesive with deionized water at 50°C for 3 days. (A) UV chromatogram at 220nm. (B) TIC full-scan MS chromatogram. (Reprinted with permission from Tiller et al., 1997a. Copyright 1997 John Wiley Sons.)...

Chemical—structural analysis and leachability tests on scum, slag, and Fe-minerals were carried out to characterize and measure the chemical stability of the metals in waste materials. The investigation was designated to (1) evaluate the... 

If a water sample contains both soluble and insoluble manganese (Mn) compounds and ions, and it is filtered to separate the dissolved and insoluble fractions, and the filtrate and insoluble residue are analyzed separately, the results can be expressed as total dissolved Mn and total suspended or insoluble Mn. Phosphorus (P) can be determined colorimet-rically as the ortho-phosphate ion, P043, in aqueous samples after a reaction that forms an intensely blue-colored derivative. However polyphosphate ions and other ions and compounds containing P do not form this derivative. Total P in a sample can be determined with the same colorimetric procedure after acid hydrolysis and oxidation of all ions and compounds containing P to P04 3. In some elemental analyses the sample is treated with reagents designed to make available for measurement some fraction of an element or elements but not the total amount. For example, a soil sample may be treated with water at pH 3 to simulate the leaching process of acid rain. A total elemental analysis of the filtrate provides information about just those elements solubilized by the mild acid treatment. This can be called the determination of total mild acid leachable elements. 

Leachability study (migration of chemicals into drug product) using LC/MS, GC/MS, ICP/AA, pH, appearance of drug and container, thermal analysis (DSC,TGA), and infrared (IR)... 

Leachables in orally inhaled and nasal drug products (OINDP) are compounds which are present in the drug product due to leaching from container closure system components. Extractables are compounds that can be extracted from OINDP device components, or surfaces of the OINDP container closure system when in presence of an appropriate solvent(s) and/or condition(s). Leachables are often a subset of, or are derived directly or indirectly from, extractables. Extractables may, therefore, be considered as potential leachables in OINDPs. Some leachables may affect product quality and/or present potential safety risks, therefore regulatory guidance has provided some recommendations regarding the analysis and toxicological safety assessment (i.e., qualification) of such compounds. 

As described above, individual packaging components will invariably contain complex mixtures of chemical entities (e.g., additives and oligomers), many if not most of which are at relatively trace levels (i.e., pg/g and lower). The principles of Trace Organic Analysis, as developed in the environmental, geochemical, and bioanalytical fields, can be applied to the problem of identification and quantification of these individual chemical entities, whether as extractables or as leachables.f The general process is as follows ... 

To be amenable to gas chromatographic analysis, a compound must volatilize without thermal decomposition and not interact with the analytical system in such a manner so as to cause irreversible surface adsorption or surface catalyzed decomposition. In addition, the polarities of the various chemical entities to be analyzed must be considered so that an appropriate GC separation mechanism (i.e., partitioning, adsorption, etc.) can be chosen. Although these factors might seem to suggest that GC is a very selective analytical technique, in fact a wide variety of chemical entities which can appear as extractables and leachables are amenable to GC separation and analysis. ... 

GC/MS can also be used to quantitate extractables and leachables with extremely high selectivity, specificity, and sensitivity. For example, Norwood et al. used GC/MS with selected ion monitoring to quantitate polycyclic aromatic hydrocarbons (PAHs) as leachables in suspension MDI drug products. The analytical method employed a cold filtration technique to remove suspended drug substance and excipients, followed by GC/MS analysis. Stable isotope labeled... 

Note that accurate mass measurements can be obtained for El and Cl as well as ESI and APCI spectra. This relatively simple example gives some idea of the power of modem MS for extractables/leachables testing, and trace organic analysis in general. Using state-of-the-art instruments, such as hybrid TOF and Fourier Transform mass... 

Numerous examples exist in the literature for LC/MS applications in pharmaceutical development, but only a few for the analysis of extractables and leachables. Of note are the works of Wu et al. who used ESI LC/MS to identify extractables from stoppers in biotech products. Tiller et alP who used data-dependent LC/MS/MS to identify leachables from adhesives used in pharmaceutical products, Castner, Williams, and Bresnick who used LC/MS to identify BHT (butyla-tedhydroxytoluene) in a lyophilized drug product, and Yu, Block, and Balagh who identified and quantified polymer additives by LC/MS. Other examples, as well as the numerous applications of HPLC to extractables/ leachables testing, have been reviewed by Jenke. " ... 

Inorganic extractables/leachables would include metals and other trace elements such as silica, sodium, potassium, aluminum, calcium, and zinc associated with glass packaging systems. Analytical techniques for the trace analysis of these elements are well established and include inductively coupled plasma—atomic emission spectroscopy (ICP-AES), ICP-MS, graphite furnace atomic absorption spectroscopy (GFAAS), electron microprobe, and X-ray fluorescence. Applications of these techniques have been reviewed by Jenke. " An example of an extractables study for certain glass containers is presented by Borchert et al. ". ... 

Physicochemical testing is performed to characterize the physical and chemical properties of a plastic to insure that the composition of the synthetic medium will not compromise the quality of the drug being stored within it. To perform these tests, samples of plastic identical to the material being used in the primary package are subjected to an extraction procedure—to dissolve in an extraction solution leachable compounds that are at risk of entering the pharmaceutical preparation. This extraction solution is then subjected to analysis to evaluate the identity and quantity of leachants. For most plastics, the appropriate extraction medium is purified water, but elastomeric closures for use with injections should include extraction with three different extraction... 

Tiller et al. demonstrated an analytical strategy with on-line LC/UV/MS and LC/MS/MS to rapidly obtain structural information for leachables from a drug-delivery device. Similar to proteomics-based applications, the analysis strategy makes use of data-dependent analysis, wherein the mass spectrometer first obtains molecular ions using full-scan techniques, and makes real-time decisions about MS/MS product-ion spectra that must be obtained. In this way, molecular weight and substructural information are both obtained for many components during a single HPLC run. 

The type of design and, especially, the material used to construct closed vessels, should be chosen as a function of the type of treatment to be applied and the subsequent type of analysis to be performed on the sample. For example, materials such as PFA (a per-fluoroalkoxy resin) and TFM [a copolymer of tetrafluoroethylene and a small amount of perfluoro(propyl vinyl ether)] should be used in the microwave digestion of samples prior to ultratrace analysis, where the material should be inert to hot concentrated acids and contain minimal amounts of leachable contaminants (28). Raster electron microscopy has shown PFA to be the most suitable material for this purpose in fact, its surface was found to remain virtually unaltered even after 100 digestion cycles [29]. 

---