The measurement of nicotine in human plasma by high-performance liquid chromatography-electrospray-tandem mass spectrometry

The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 muL) with added deuterium-labeled d(3)-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 mL) followed by back-extraction into 0.1% formic acid (50 muL). Chromatography was performed on a phenyl Novapak column with a mobile phase consisting of 50% 10 mM ammonium fortriate (pH 3.3) and acetonitrile (50:50, vol/vol). A flow rate of 0.2 mL/min resulted in a total analysis time of 5 minutes per sample. Mass spectrometric detection was by selected reactant monitoring (nicotine m/z 163.2 --> 130.2; IS m/z 166.2 --> 87.2). The assay was linear from 0.5 to 100 mug/L (r > 0.993, n = 9). The accuracy and imprecision of the method for quality control sampleswere 87.5% to 113% and < 10.2%, respectively. Interday accuracy and imprecision at the limit of quantification (0.5 mug/L) was 113% and 7.2% (n = 4). The process efficiency for nicotine in plasma was > 75%. The method described has good process efficiency, stabilized nicotine, avoided concentration steps, and most importantly minimized potential contamination. Further, we have established that water-based standards and controls are interchangeable with plasma-based samples. This method was used successfully to measure the pharmacokinetic profiles of subjects involved in the development of an aerosol inhalation drug delivery system.

High-fidelity Z-measurement error encoding of optical qubits

We demonstrate a quantum error correction scheme that protects against accidental measurement, using a parity encoding where the logical state of a single qubit is encoded into two physical qubits using a nondeterministic photonic controlled-NOT gate. For the single qubit input states vertical bar 0 >, vertical bar 1 >, vertical bar 0 > +/- vertical bar 1 >, and vertical bar 0 > +/- i vertical bar 1 > our encoder produces the appropriate two-qubit encoded state with an average fidelity of 0.88 +/- 0.03 and the single qubit decoded states have an average fidelity of 0.93 +/- 0.05 with the original state. We are able to decode the two-qubit state (up to a bit flip) by performing a measurement on one of the qubits in the logical basis; we find that the 64 one-qubit decoded states arising from 16 real and imaginary single-qubit superposition inputs have an average fidelity of 0.96 +/- 0.03.

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi(2) = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male nonsmokers (adjusted beta = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta = -0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta 2-microglobutin (P = 0.02) and N-acetyl-beta-D-glucosaminidase (P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi(2) = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Equilibrium swelling measurements of network and semicrystalline polymers in supercritical carbon dioxide using high-pressure NMR

The extent of swelling of cross-linked poly(dimethylsiloxane) and linear low-density poly(ethylene) in supercritical CO2 has been investigated using high-pressure NMR spectroscopy and microscopy. Poly(dimethylsiloxane) was cross-linked to four different cross-link densities and swollen in supercritical CO2. The Flory-Huggins interaction parameter, x, was found to be 0.62 at 300 bar and 45 degrees C, indicating that supercritical CO2 is a relatively poor solvent compared to toluene or benzene. Linear low-density poly(ethylene) was shown to exhibit negligible swelling upon exposure to supercritical CO2 up to 300 bar. The effect Of CO2 pressure on the amorphous region of the poly(ethylene) was investigated by observing changes in the H-1 T-2 relaxation times of the polymer. These relaxation times decreased with increasing pressure, which was attributed to a decrease in mobility of the polymer chains as a result of compressive pressure.

Significance of frictional heating for effects of high pressure homogenisation on milk

High pressure homogenisation (HPH) is a novel dairy processing tool, which has many effects on enzymes, microbes, fat globules and proteins in milk. The effects of HPH on milk are due to a combination of shear forces and frictional heating of the milk during processing; the relative importance of these different factors is unclear, and was the focus of this study. The effect of milk inlet temperature (in the range 10-50 degrees C) on residual plasmin, alkaline phosphatase, lactoperoxidase and lipase activities in raw whole bovine milk homogenised at 200 MPa was investigated. HPH caused significant heating of the milk; outlet temperature increased in a linear fashion (0(.)5887 degrees C/degrees C, R-2 =0-9994) with increasing inlet temperature. As milk was held for 20 s at the final temperature before cooling, samples of the same milk were heated isothermally in glass capillary tubes for the same time/temperature combinations. Inactivation profiles of alkaline phosphatase in milk were similar for isothermal heating or HPH, indicating that loss of enzyme activity was due to heating alone. Loss of plasmin and lactoperoxidase activity in HPH milk, however, was greater than that in heated milk. Large differences in residual lipase activities in milks subjected to heating or HPH were observed due to the significant increase in lipase activity in homogenised milk. Denaturation of beta-lactoglobulin was more extensive following HPH than the equivalent heat treatment. Inactivation of plasmin was correlated with increasing fat/serum interfacial area but was not correlated with denaturation of beta-lactoglobulin. Thus, while some effects of HPH on milk are due to thermal effects alone, many are induced by the combination of forces and heating to which the milk is exposed during HPH.

A theoretical comparison of two optimization methods for radiofrequency drive schemes in high frequency MRI resonators

In this paper, numerical simulations are used in an attempt to find optimal Source profiles for high frequency radiofrequency (RF) volume coils. Biologically loaded, shielded/unshielded circular and elliptical birdcage coils operating at 170 MHz, 300 MHz and 470 MHz are modelled using the FDTD method for both 2D and 3D cases. Taking advantage of the fact that some aspects of the electromagnetic system are linear, two approaches have been proposed for the determination of the drives for individual elements in the RF resonator. The first method is an iterative optimization technique with a kernel for the evaluation of RF fields inside an imaging plane of a human head model using pre-characterized sensitivity profiles of the individual rungs of a resonator; the second method is a regularization-based technique. In the second approach, a sensitivity matrix is explicitly constructed and a regularization procedure is employed to solve the ill-posed problem. Test simulations show that both methods can improve the B-1-field homogeneity in both focused and non-focused scenarios. While the regularization-based method is more efficient, the first optimization method is more flexible as it can take into account other issues such as controlling SAR or reshaping the resonator structures. It is hoped that these schemes and their extensions will be useful for the determination of multi-element RF drives in a variety of applications.

Kinetic study of the thermal degradation of high density polyethylene

The thermal degradation of high density polyethylene has been modelled by the random breakage of polymer bonds, using a set of population balance equations. A model was proposed in which the population balances were lumped into representative sizes so that the experimentally determined molecular weight distribution of the original polymer could be used as the initial condition. This model was then compared to two different cases of the unlumped population balance which assumed unimolecular initial distributions of 100 and 500 monomer units, respectively. The model that utilised the experimentally determined molecular weight distribution was found to best describe the experimental data. The model fits suggested a second mechanism in addition to random breakage at slow reaction rates. (c) 2005 Elsevier Ltd. All rights reserved.

Non-linear photoluminescence from purified aqueous PbS nanocrystals

A simple and effective method for purifying photoluminescent water-soluble surface passivated PbS nanocrystals has been developed. Centrifuging at high speeds removes PbS nanocrystals that exhibit strong red band edge photoluminescence from an original solution containing multiple nanocrystalline species with broad photoluminescence spectra. The ability to purify the PbS nanocrystals allowed two-photon photoluminescence spectroscopy to be performed on water-soluble PbS nanocrystals and be attributed to band edge recombination. (c) 2006 Elsevier B.V. All rights reserved.

Measurement and stability of FTY720 in human whole blood by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

We report here a validated method for the quantification of a new immunosuppressant drug FTY720, using HPLC-tandem mass spectrometry. Whole blood samples (500 mu l) were subjected to liquid-liquid extraction, in the presence of an internal standard (Y-32919). Mass spectrometric detection was by selected reaction monitoring with an atmospheric pressure chemical ionization source in positive ionization mode (FTY720: m/z 308.3 -> 255.3). The assay was linear from 0.2 to 25 mu g/l (r(2) > 0.997, n = 5). The inter- and intra-day analytical recovery and imprecision for quality control samples (0.5, 7 and 15 mu g/l) were 95.8-103.2 and < 5.5%, respectively. At the lower limit of quantification (0.2 mu g/l) the interand intra-day analytical recovery was 99.0-102.8% with imprecision of < 7.6% (n = 5). The assay had a mean relative recovery of 100.5 +/- 5.8% (n = 15). Extracted samples were stable for 16 h. IFTY720 quality control samples were stable at room temperature for 16 h at 4 degrees C for at least 8 days and when taken through at least three freeze-thaw cycles. In conclusion, the method described displays analytical performance characteristics that are suitable for pharmacokinetic studies in humans. (c) 2006 Elsevier B.V. All rights reserved.

Size-corrected BMD decreases during peak linear growth: Implications for fracture incidence during adolescence

Peak adolescent fracture incidence at the distal end of the radius coincides with a decline in size-corrected BMD in both boys and girls. Peak gains in bone area preceded peak gains in BMC in a longitudinal sample of boys and girls, supporting the theory that the dissociation between skeletal expansion and skeletal mineralization results in a period of relative bone weakness. Introduction: The high incidence of fracture in adolescence may be related to a period of relative skeletal fragility resulting from dissociation between bone expansion and bone mineralization during the growing years. The aim of this study was to examine the relationship between changes in size-corrected BMD (BMDsc) and peak distal radius fracture incidence in boys and girls. Materials and Methods: Subjects were 41 boys and 46 girls measured annually (DXA; Hologic 2000) over the adolescent growth period and again in young adulthood. Ages of peak height velocity (PHV), peak BMC velocity (PBMCV), and peak bone area (BA) velocity (PBAV) were determined for each child. To control for maturational differences, subjects were aligned on PHV. BMDsc was calculated by first regressing the natural logarithms of BMC and BA. The power coefficient (pc) values from this analysis were used as follows: BMDsc = BMC/BA(pc). Results: BMDsc decreased significantly before the age of PHV and then increased until 4 years after PHV. The peak rates in radial fractures (reported from previous work) in both boys and girls coincided with the age of negative velocity in BMDsc; the age of peak BA velocity (PBAV) preceded the age of peak BMC velocity (PBMCV) by 0.5 years in both boys and girls. Conclusions: There is a clear dissociation between PBMCV and PBAV in boys and girls. BMDsc declines before age of PHV before rebounding after PHV. The timing of these events coincides directly with reported fracture rates of the distal end of the radius. Thus, the results support the theory that there is a period of relative skeletal weakness during the adolescent growth period caused, in part, by a draw on cortical bone to meet the mineral demands of the expanding skeleton resulting in a temporary increased fracture risk.

Synthesis of monocyclic and linear polystyrene using the reversible coupling/cleavage of thiol/disulfide groups

By carefully controlling the concentration of alpha,omega-thiol polystyrene in solution, we achieved formation of unique monocyclic polystyrene chains (i.e., polymer chains with only one disulfide linkage). The presence of cyclic polystyrene was confirmed by its lower than expected molecular weight due to a lower hydrodynamic volume and loss of thiol groups as detected by using Ellman's reagent. The alpha,omega-thiol polystyrene was synthesized by polymerizing styrene in the presence of a difunctional RAFT agent and subsequent conversion of the dithioester end groups to thiols via the addition of hexylamine. Oxidation gave either monocyclic polymer chains (i.e., with only one disulfide linkage) or linear multiblock polymers with many disulfide linkages depending on the concentration of polymer used with greater chance of cyclization in more dilute solutions. At high polymer concentrations, linear multiblock polymers were formed. To control the MWD of these linear multiblocks, monofunctional X-PSTY (X = PhCH2C(S)-S-) was added. It was found that the greatest ratio of X-PSTY to X-PSTY-X resulted in a low M-n and PDI. We have shown that we can control both the structure and MWD using this chemistry, but more importantly such disulfide linkages can be readily reduced back to the starting polystyrene with thiol end groups, which has potential use for a recyclable polymer material.

High fidelity radiation pattern measurement system for small antennas

The paper describes a high fidelity system for measuring a radiation pattern of an electrically small antenna. In this system, the Antenna Under Test (AUT) equipped with a battery powered signal generator is suspended by a dielectric foam in the centre of a pair of dielectric rings that are supported by a pedestal of a spherical positioning mechanical sub-system. Radiation patterns are obtained directly in spherical format using a suitably constructed probe antenna of linear or circular polarization. Measurements are controlled by a computer, which also stores and processes the measured data. The results reveal considerable differences between the radiation patterns of a small antenna obtained using the proposed wireless approach and the conventional one, in which the antenna is connected with a cable to the receiver.