The analysis of acetaminophen (paracetamol) and seven metabolites in rat, pig and human plasma by U(H)PLC–MS

A U(H)PLC–MS/MS method is described for the analysis of acetaminophen and its sulphate, glucuronide, glutathione, cysteinyl and N-acetylcysteinyl metabolites in plasma using stable isotope-labeled internal standards. P-Aminophenol glucuronide and 3-methoxyacetaminophen were monitored and semi-quantified using external standards. The assay takes 7.5 min/sample, requires only 5 μl of plasma and involves minimal sample preparation. The method was validated for rat plasma and cross validated for human and pig plasma and mouse serum. LOQ in plasma for these analytes were 0.44 μg/ml (APAP-C), 0.58 μg/ml (APAP-SG), 0.84 μg/ml (APAP-NAC), 2.75 μg/ml (APAP-S), 3.00 μg/ml (APAP-G) and 16 μg/ml (APAP). Application of the method is illustrated by the analysis of plasma following oral administration of APAP to male Han Wistar rats

The analysis of acetaminophen (paracetamol) and seven metabolites in rat, pig and human plasma by U(H)PLC–MS

A U(H)PLC–MS/MS method is described for the analysis of acetaminophen and its sulphate, glucuronide, glutathione, cysteinyl and N-acetylcysteinyl metabolites in plasma using stable isotope-labeled internal standards. P-Aminophenol glucuronide and 3-methoxyacetaminophen were monitored and semi-quantified using external standards. The assay takes 7.5 min/sample, requires only 5 μl of plasma and involves minimal sample preparation. The method was validated for rat plasma and cross validated for human and pig plasma and mouse serum. LOQ in plasma for these analytes were 0.44 μg/ml (APAP-C), 0.58 μg/ml (APAP-SG), 0.84 μg/ml (APAP-NAC), 2.75 μg/ml (APAP-S), 3.00 μg/ml (APAP-G) and 16 μg/ml (APAP). Application of the method is illustrated by the analysis of plasma following oral administration of APAP to male Han Wistar rats

Metabolism and Effects on Endogenous Metabolism of Paracetamol (Acetaminophen) in a Porcine Model of Liver Failure

The metabolic fate, toxicity and effects on endogenous metabolism of paracetamol (acetaminophen, APAP) in 22 female Landrace cross large white pigs were evaluated in a model of acute liver failure (ALF). Anaesthetized pigs were initially dosed at 250 mg/kg via an oroduodenal tube with APAP serum concentrations maintained above 300 mg/L using maintenance doses of 0.5-4g/h until ALF. Studies were undertaken to determine both the metabolic fate of APAP and its effects on the endogenous metabolic phenotype of ALF in using 1H NMR spectroscopy. Increased concentrations of citrate combined with pre-ALF increases in circulating lactate, pyruvate and alanine in plasma suggest mitochondrial dysfunction and a switch in hepatic energy metabolism to glycolysis in response to APAP treatment. A specific liquid chromatography-tandem mass spectrometry assay was used to quantify APAP and metabolites. The major circulating and urinary metabolite of APAP was the phenolic glucuronide (APAP-G), followed by p-aminophenol glucuronide (PAP-G) formed from N-deacetylated APAP. The PAP produced by N-deacetylation was the likely cause of the methaemoglobinemia and kidney toxicity observed in this, and previous, studies in the pig. The phenolic sulfate of APAP, and the glutathione-derived metabolites of the drug were only found as minor components (with the cysteinyl conjugate detected but not the mercapturate). Given its low sulfation, combined with significant capacity for N-deacetylation the pig may represent a poor translational model for toxicology studies for compounds undergoing significant metabolism by sulfation, or which contain amide bonds which when hydrolysed to unmask an aniline lead to toxicity. However, the pig may provide a useful model where extensive amide hydrolysis is seen for drugs or environmental chemicals in humans, but not in e.g., the rat and dog which are the pre-clinical species normally employed for safety assessment

The effect of specimen dimensions on obtained tensile properties of sheet metals

A pilot study has been carried out to examine the effect of specimen dimensions on the obtained tensile properties of aluminium and steel sheet. The materials used were DP600 grade steel and AA5754 grade aluminium sheet. Four types of dog-bone samples with varying dimensions were tested for both materials. Standard tensile test procedures were performed using a universal test machine together with contacting extensometry. The GOM Aramis photogrammetric 2D strain mapping technique was also applied. The results suggest that for both steel and aluminium sheet materials, differing specimen dimensions have little effect on the obtained mechanical properties. Depending on the gauge length of extensometer chosen and the position at where necking occurred on the sample, the extensometry results and 2D strain mapping results slightly differed towards to the end of stress-strain curve. The failure mode between the chosen grades of steel and aluminium, samples was observed to differ, as did the percentage of failures that occurred within the gauge length. All steel samples fractured across the specimen perpendicularly to the test direction; whilst fracture of aluminium samples occurred approximately 30 degrees from the perpendicular

Hole Expansion of Aluminum Alloys for the Automotive Industry

The introduction of Aluminum alloys in the automotive industry due to their high strength-to-weight ratio has brought with it a number of technical hurdles which require overcoming in order that their full potential may be realized. One of the issues that require addressing is that of edge cracking, a phenomenon which is particularly difficult to predict. This is often observed during the initial drawing operation in a traditional automotive stamping plant. A useful measure of a materials susceptibility to edge cracking is the Hole Expansion Ratio. Currently there is a standard (ISO 16630) which provides for holes to be expanded by a conical punch, where the original hole is introduced via punching. This reflects the traditional processing route within the automotive industry. Investigations have been conducted using both conical and flat-topped punches, as well as using drilling and reaming, and CNC machining to introduce the initial hole for comparison with the standard punched route in order to understand the effect of different processes on the susceptibility to edge cracking. The hole expansion ratio for a number of aluminum alloys, both 5xxx and 6xxx series, has been determined. Regression analyses of hole expansion ratios against material thickness and UTS have been conducted, and a relationship has been established for the different punch and hole types. Consideration is also given to combining a materials hole expansion ratio with its Forming Limit Curve (FLC), with a focus on tool design and tool buy-off being presented

Experimental Evaluation of Springback in Aluminium Alloys Using Optical Measurement and Numerical Analysis

The aim of this paper is to establish an efficient and effective means of understanding the springback behaviour of a 5xxx-O and a 6xxx-T61 series aluminium alloy. The tooling used for investigating the springback is a small U-channel stamping draw die using two die radii of 8 or 12 mm and a punch radius of 12 mm. The samples were drawn to depths of 50 or 75 mm with a minimum of 5 samples being drawn for each condition. The U-channel samples were then evaluated using an optical scanning technique and the springback values were calculated using a numerical analysis as developed by one of the authors. The comparison of the sidewall springback, sidewall curl and flange springback under different conditions is conducted and the effect of the draw depth and die radius on the final springback is shown. Statistical analyses of both the drawing condition and the scanning technique are conducted to understand the effect of process variation on the results obtained. The 6xxx series shows higher springback values when compared to 5xxx series alloy. An increase in drawing depth suggests higher springback for both the alloys

60 solvent compounding of natural fibre reinforced polymer composite systems

The traditional methods of combining fibrous reinforcement with resin matrix have been dictated by the properties of the matrix. If a thermoset matrix is used the low viscosity of the unreacted system can be exploited to either mix in quantities of short fibre reinforcement, as with bulk moulding compound, or to infiltrate the resin through reinforcement as with resin transfer moulding, however it is necessary to ensure that the moulded article is formed into its final shape before the resin cures. If a thermoplastic resin is selected then the high viscosity of material means that the blending of reinforcement and fibre must usually be performed under condition of high temperature and shear, as for example by compounding extruder or calendaring. This paper describes a method of exploiting the soluble nature of certain biodegradable polymers to produce an injection mouldable short fibre reinforced material without a mechanical compounding stage. This method combines the low viscosity advantages of thermoset systems with the continuing mouldability of thermoplastics. It is anticipated that this method will allow the production of mouldable compounds on the farm, thus allowing the grower to benefit from the higher value of a semi-finished produc

In mould painting using thermoset powder coating and thermoplastic substrate in closed tool injection moulding

In mould decoration (IMD) is attractive because a fully, or partially, decorated component is produced directly from the moulding process, with reduced emissions at lower process costs when compared to traditional techniques. A new IMD process has been developed to produce a painted component direct from the injection moulding tool. This incorporates the pressure spraying of thermoset powders through a valve into a closed mould. The residual heat of the tool initially softens the thermoset. The high temperature of thermoplastic polymer injected in a standard injection moulding subsequently cures the thermoset. The resultant product combines both thermoplastic and thermoset in a single injection moulding cycle. This paper presents frames from high speed video capture of powder mould filling and the results of INSPIRE ( in mould spray painting, impact reduced on the environment) initial injection moulding using thermoset polyester and acrylonitrile butadiene styrene (ABS). The parameters that affect material distribution are examined and discussed. Similarities to the coinjection moulding process are noted