A comparison of the quantitative methods for the analysis of the platinum-containing anticancer drug [cis-[amminedichloro(2-methylpyridine)]platinum(II)] (ZD0473) by HPLC coupled to either a triple quadrupole mass spectrometer or an inductively coupled plasma mass spectrometer

The use of high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICPMS) as means for the quantitative determination of ZD0473, a platinum anticancer drug, and its related biologically active "aqua" compounds in biofluid samples is described. The performance of the resulting HPLC-ICPMS method was compared with that of a conventional HPLC-triple quadrupole mass spectrometer-based (HPLC-MS/MS) system for properties such as limit of detection, linearity, and reproducibility using spiked samples. The methods were then applied to the determination of plasma ultrafitrate concentrations of ZD0473 in dog plasma samples obtained following intravenous and oral administration at 0.5 and 6 mg/kg, respectively. These experiments showed that both methods were capable of providing accurate and precise results but that the HPLC-ICPMS method had advantages of extended linear range and superior sensitivity, providing a limit of quantification of 0.1 ng/mL for ZD0473, as compared to 5 ng/mL using the current HPLC-MS/MS method. In addition, by using a single combined HPLC-ICPMS/MS/MS system, it was possible to determine the relative MS/MS response of the aqua compounds for the first time.     

Bioanalytical and chemical assessment of the disinfection by-product formation potential: Role of organic matter

Disinfection by-products (DBP) formed from natural organic matter and disinfectants like chlorine and chloramine may cause adverse health effects. Here, we evaluate how the quantity and quality of natural organic matter and other precursors influence the formation of DBPs during chlorination and chloramination using a comprehensive approach including chemical analysis of regulated and emerging DBPs, total organic halogen quantification, organic matter characterisation and bioanalytical tools. In vitro bioassays allow us to assess the hazard potential of DBPs early in the chain of cellular events, when the DBPs react with their molecular target(s) and activate stress response and defence mechanisms. Given the reactive properties of known DBPs, a suite of bioassays targeting reactive modes of toxic action including genotoxicity and sensitive early warning endpoints such as protein damage and oxidative stress were evaluated in addition to cytotoxicity. Coagulated surface water was collected from three different drinking water treatment plants, along with reverse osmosis permeate from a desalination plant, and DBP formation potential was assessed after chlorination and chloramination. While effects were low or below the limit of detection before disinfection, the observed effects and DBP levels increased after disinfection and were generally higher after chlorination than after chloramination, indicating that chlorination forms higher concentrations of DBPs or more potent DBPs in the studied waters. Bacterial cytotoxicity, assessed using the bioluminescence inhibition assay, and induction of the oxidative stress response were the most sensitive endpoints, followed by genotoxicity. Source waters with higher dissolved organic carbon levels induced increased DBP formation and caused greater effects in the endpoints related to DNA damage repair, glutathione conjugation/protein damage and the Nrf2 oxidative stress response pathway after disinfection. Fractionation studies indicated that all molecular weight fractions of organic carbon contributed to the DBP formation potential, with the humic rich fractions forming the greatest amount of DBPs, while the low molecular weight fractions formed more brominated DBPs due to the high bromide to organic carbon ratio. The presence of higher bromide concentrations also led to a higher fraction of brominated DBPs as well as proportionally higher effects. This study demonstrates how a suite of analytical and bioanalytical tools can be used to effectively characterise the precursors and formation potential of DBPs.     

A screening level fate model of organic contaminants from advanced water treatment in a potable water supply reservoir

Augmentation of potable water sources by planned indirect potable reuse of wastewater is being widely considered to address growing water shortages. Environmental buffers such as lakes and dams may act as one of a series of barriers to potable water contamination stemming from micropollutants in wastewater. In South-East Queensland, Australia, current government policy is to begin indirect potable reuse of water from reverse osmosis equipped advanced water treatment plants (AWTPs) when the combined capacity of its major storages is at 40% capacity. A total of 15 organic contaminants including NDMA and bisphenol A have been publically reported as detected in recycled water from one of South-East Queensland’s AWTPs, while another 98 chemicals were analysed for, but found to be below their detection limit. To assess the natural attenuation in Lake Wivenhoe, a Level III fugacity based evaluative fate model was constructed using the maximum concentrations of these contaminants detected as input data. A parallel aquivalence based model was constructed for those contaminants, such as dichloroacetic acid, dalapon and triclopyr, which are ionised in the environment of Lake Wivenhoe. A total of 247 organic chemicals of interest, including disinfection by-products, pesticides, pharmaceuticals and personal care products, xenoestrogens and industrial chemicals, were evaluated with the model to assess their potential for natural attenuation. Out of the 15 detected chemicals, trihalomethanes are expected to volatilise with concentrations in the outflow from the dam approximately 400 times lower than influent from the AWTPs. Transformation processes in water are likely to be more significant for NDMA and pharmaceuticals such as salicylic acid and paracetamol as well as for caffeine and the herbicides dalapon and triclopyr. For hydrophobic contaminants such as cholesterol and phenolic xenoestrogens such as 4-nonylphenol, 4-t-octylphenol and bisphenol A, equilibrium between water and sediments will not be attained and hence fate processes such as removal in outflow are predicted to become relatively important.     

Natural versus wastewater derived dissolved organic carbon: implications for the environmental fate of organic micropollutants

The interaction of organic micropollutants with dissolved organic carbon (DOC) can influence their transport, degradation and bioavailability. While this has been well established for natural organic carbon, very little is known regarding the influence of DOC on the fate of micropollutants during wastewater treatment and water recycling. Dissolved organic carbon-water partition coefficients (K_DOC) for wastewater derived and reference DOC were measured for a range of micropollutants using a depletion method with polydimethylsiloxane disks. For micropollutants with an octanol-water partition coefficient (log K_OW) greater than 4 there was a significant difference in K_DOC between reference and wastewater derived DOC, with partitioning to wastewater derived DOC over 1000 times lower for the most hydrophobic micropollutants. The interaction of nonylphenol with wastewater derived DOC from different stages of a wastewater and advanced water treatment train was studied, but little difference in K_DOC was observed. Organic carbon characterisation revealed that reference and wastewater derived DOC had very different properties due to their different origins. Consequently, the reduced sorption capacity of wastewater derived DOC may be related to their microbial origin which led to reduced aromaticity and lower molecular weight. This study suggests that for hydrophobic micropollutants (log K_OW > 4) a higher concentration of freely dissolved and thus bioavailable micropollutants is expected in the presence of wastewater derived DOC than predicted using K_DOC values quantified using reference DOC. The implication is that naturally derived DOC may not be an appropriate surrogate for wastewater derived DOC as a matrix for assessing the fate of micropollutants in engineered systems.     

Development of a new synthetic bone graft

A process for the replication of bovine cancellous bone in synthetic bioceramic materials for use as artificial bone graft substitutes is described. The process detailed here may be easily implemented to allow production of large numbers of blocks of material, even on a laboratory scale. The graft material has a pore morphology and interconnectivity identical with that of the original cancellous bone used as a starting material. Strength of the material is adequate, and at lower porosity levels it meets the FDA requirements for coralline materials for spinal applications. The synthetic graft is also shown to have excellent fluid-retention characteristics, making it a potential carrier for morphogenic agents such as solutions of bone morphogenic protein. © 1998 Kluwer Academic Publishers/p>     

Pro-labour myometrial gene expression: are preterm labour and term labour the same?

Preterm labour (PTL) is the most important cause of neonatal morbidity and mortality. While some causes have been identified, the mechanisms involved remain elusive. This study investigates whether term labour (TL) is an appropriate model for PTL by examining pro-labour gene expression, using quantitative rtPCR, and protein synthesis, using Western analysis, in preterm and term myometrial samples obtained from the upper and lower uterine segments before and after the onset of labour. In the lower segment, the levels of prostaglandin H synthase type-2 (PGHS-2), interleukin-1beta (IL-1beta), IL-6 and IL-8 mRNA expression were significantly higher in TL compared with PTL samples. Compared with non-labour controls, the expression of IL-1beta and IL-8 mRNA was increased in both PTL and TL samples and the expression of PGHS-2 and IL-6 mRNA was increased in TL samples only. In the upper segment, there were no differences between PTL and TL samples and the mRNA expression of PGHS-2 and IL-1beta was increased in TL compared with term no labour samples. No effect of PTL or TL was seen on either oxytocin receptor or connexin-43 mRNA expression or protein levels. The multiple regression analysis and studies in primary cultures of uterine myocytes suggest that the inflammatory cytokines, IL-1beta and tumour necrosis factor-alpha, are the most important regulators of PGHS-2 and IL-8. Our data show that preterm and term labouring myometrium are significantly different and that the most marked labour-induced changes in gene expression are in the lower segment. These changes may occur in response to the release of inflammatory cytokines by the labour-associated inflammatory infiltration.     

High intensity compounding of mica-filled thermoplastics

High-speed turbine mixers have been adapted for compounding filled thermoplastics by the partial flux method. The extreme shearing forces exerted by the mixing impellors simultaneously mixes and delaminates mica fillers to form finely dispersed compounds in a granular, partially fused state which can be directly injection molded without pelletizing. In practice, one turbine mixing unit can be employed for compounding all types of resins and fillers. The partial flux method permits compounding to be accomplished at peak sensor temperatures that are considerably below the resin softening or melting transitions, frequently 50°C less than normal compounding temperatures. The short residence times and reduced energy requirements possible with partial fluxing results in substantial cost reduction without compromising quality or performance. Examples are provided for polypropylene, nylon 66, poly(butene terephthalate), poly(ethylene terephthalate) and poly(phenylene oxide) alloys. Impact modifiers derived from carboxylated polyolefin waxes may be dispersed by the intense shearing action to form highly subdivided submicron particles, which promote crazing and shear deformation during fracture testing, thereby contributing to increased composited toughness with minor sacrifice in modulus and strength. The mechanical properties of micafilled thermoplastics have also been compared with those of short glass fiber composites. In certain applications requiring stiffness and dimensional stability at elevated temperatures, mica composites prepared by intensive mixing in a turbine mixer may be economically substituted for glass fiber counterparts.     

Bioanalytical assessment of the formation of disinfection byproducts in a drinking water treatment plant

Disinfection of drinking water is the most successful measure to reduce water-borne diseases and protect health. However, disinfection byproducts (DBPs) formed from the reaction of disinfectants such as chlorine and monochloramine with organic matter may cause bladder cancer and other adverse health effects. In this study the formation of DBPs through a full-scale water treatment plant serving a metropolitan area in Australia was assessed using in vitro bioanalytical tools, as well as through quantification of halogen-specific adsorbable organic halogens (AOXs), characterization of organic matter, and analytical quantification of selected regulated and emerging DBPs. The water treatment train consisted of coagulation, sand filtration, chlorination, addition of lime and fluoride, storage, and chloramination. Nonspecific toxicity peaked midway through the treatment train after the chlorination and storage steps. The dissolved organic matter concentration decreased after the coagulation step and then essentially remained constant during the treatment train. Concentrations of AOXs increased upon initial chlorination and continued to increase through the plant, probably due to increased chlorine contact time. Most of the quantified DBPs followed a trend similar to that of AOXs, with maximum concentrations observed in the final treated water after chloramination. The mostly chlorinated and brominated DBPs formed during treatment also caused reactive toxicity to increase after chlorination. Both genotoxicity with and without metabolic activation and the induction of the oxidative stress response pathway showed the same pattern as the nonspecific toxicity, with a maximum activity midway through the treatment train. Although measured effects cannot be directly translated to adverse health outcomes, this study demonstrates the applicability of bioanalytical tools to investigate DBP formation in a drinking water treatment plant, despite bioassays and sample preparation not yet being optimized for volatile DBPs. As such, the bioassays are useful as monitoring tools as they provide sensitive responses even at low DBP levels.