Rapid and sensitive determination of acetylsalicylic acid and salicylic acid in plasma using liquid chromatography–tandem mass spectrometry: application to pharmacokinetic study

A simple and sensitive analytical method using liquid chromatography–tandem mass spectrometry (LC/MS/MS) for determination of acetylsalicylic acid (aspirin, ASA) and its major metabolite, salicylic acid (SA), in animal plasma has been developed and validated. Both ASA and SA in plasma samples containing potassium fluoride were extracted using acetonitrile (protein precipitation) with 0.1% formic acid in it. 6‐Methoxysalicylic acid was used as the internal standard (IS). The compounds were separated on a reversed‐phase column. The multiple reaction monitoring mode was used with ion transitions of m/z 178.9 → 136.8, 137.0 → 93.0 and 167.0 → 123.0 for ASA, SA and IS, respectively. The lower limits of quantification for ASA and SA were 3 and 30 ng/mL, respectively. The developed method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after p.o. and i.v. administration of 1 mg/kg to rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Excitation and relative differential oscillator strengths for trifluoromethyl sulphur pentafluoride, SF5CF3, in the UV–VUV region by electron energy loss spectroscopy

Electron energy loss spectroscopy (EELS) has been used to study the photo-absorption spectrum of trifluoromethyl sulphur pentafluoride (SF₅CF₃) for the first time. Comparison is made with the EELS spectrum of sulphur hexafluoride (SF₆). The photolysis of the compound is discussed with relevance to estimated lifetimes in the atmosphere. It is estimated that the lifetime of SF₅CF₃ is of the order of 1000 years.     

Evaluation of Raman probe for oesophageal cancer diagnostics

Early detection of (pre-)cancerous changes improves prognosis, therefore in the UK patients at high risk of developing gastrointestinal cancers are enrolled on endoscopic surveillance programmes or the Bowel Cancer Screening Programme. The current gold standard technique for the detection of pre-cancerous changes in the gastrointestinal tract is histopathological analysis of biopsy tissue collected at endoscopy. This relies upon subjective assessment of morphological changes within the excised tissue samples and poor targeting of pre-malignant lesions. Raman spectroscopy offers a number of potential advantages for in vivo assessment of tissue at endoscopy. The performance of a custom built Raman probe as a biopsy targeting tool has been evaluated using excised biopsy material. Multivariate classification models have been used to demonstrate the likely ability of a miniature, confocal, fibre optic Raman probe to be used as an optical biopsy tool at endoscopy to provide spectral information in clinically practicable timescales. This technique could facilitate improved targeting of excisional biopsy with associated clinical benefits.     

Raman spectroscopy--a new method for the intra-operative assessment of axillary lymph nodes

Sentinel Lymph Node Biopsy has become the standard surgical procedure for the sampling of axillary lymph nodes in breast cancer. Intra operative node assessment is currently not offered to the majority of patients but would allow definitive axillary surgery to take place immediately. This would confer benefits both to the patient and to the healthcare system. Our experimental study aims to demonstrate that a Raman spectroscopy probe device could overcome many of the disadvantages of current intra-operative analysis techniques. 38 axillary lymph nodes, 25 negative and 13 positive from 20 patients undergoing breast surgery for invasive breast cancer were assessed using a commercially available Raman spectroscopy probe. Spectra were assessed using principal component fed linear discriminant analysis trained by the histopathology results. Leave one node out cross validation achieved a sensitivity of up to 92% and a specificity of up to 100% in differentiating between normal and metastatic lymph nodes.     

Space Research: Particles and their Fields A Brief Introduction for Mathematicians

The use of vectors in describing the motion of charged particles is illustrated by applying the results of an elementary analysis to the motions of charged particles in Earth's ionosphere and magnetosphere. In the ionosphere electric fields give rise to ‘E x B’ drifts which cause bulk motion of the ionization away from the equator near midday. This is evident in world contours of the isolines of electron density which exhibit an equatorial trough near noon and in the early afternoon. In the magnetosphere, drifts caused by particle pressures, together with inhomogeneity and curvature drifts, cause the charged particles there to form a geomagnetic ring current whose effects have been observed by satellite. This ring current may affect the topology of the magnetosphere.     

A Building Block Approach for the Total Synthesis of YM-385781

YM-254890 and FR900359 are potent and selective inhibitors of the Gq/11-signaling pathway. As such, they have been attractive targets for both synthesis and biological studies. Yet in spite of this effort, a versatile synthetic approach to the molecules that allows for the rapid construction of a variety of non-natural and labelled analogs and an increase in the amount of those analogs available remains elusive. We report here a convergent building block approach to the molecules that can solve this challenge.     

Self-Assembled Surfactant-Polyoxovanadate Soft Materials as Tuneable Vanadium Oxide Cathode Precursors for Lithium-Ion Batteries

The mixing of [V₁₀O₂₈]⁶⁻ decavanadate anions with a dicationic gemini surfactant ( gem ) leads to the spontaneous self-assembly of surfactant-templated nanostructured arrays of decavanadate clusters. Calcination of the material under air yields highly crystalline, sponge-like V₂O₅ ( gem -V₂O₅ ). In contrast, calcination of the amorphous tetrabutylammonium decavanadate allows isolation of a more agglomerated V₂O₅ consisting of very small crystallites ( TBA -V₂O₅ ). Electrochemical analysis of the materials’ performance as lithium-ion intercalation electrodes highlights the role of morphology in cathode performance. The large crystallites and long-range microstructure of the gem -V₂O₅ cathode deliver higher initial capacity and superior capacity retention than TBA -V₂O₅ . The smaller crystallite size and higher surface area of TBA -V₂O₅ allow faster lithium insertion and superior rate performance to gem -V₂O₅ .     

Gas and Particle Dynamics of a Contoured Shock Tube for Pre-clinical Microparticle Drug Delivery

We investigate the gas-particle dynamics of a device designed for biological pre-clinical experiments. The device uses transonic/supersonic gas flow to accelerate microparticles such that they penetrate the outer skin layers. By using a shock tube coupled to a correctly expanded nozzle, a quasi-one-dimensional, quasi-steady flow (QSF) is produced to uniformly accelerate the microparticles. The system utilises a microparticle “cassette” (a diaphragm sealed container) that incorporates a jet mixing mechanism to stir the particles prior to diaphragm rupture. Pressure measurements reveal that a QSF exit period – suitable for uniformly accelerating microparticles – exists between 155 and 220 mus after diaphragm rupture. Immediately preceding the QSF period, a starting process secondary shock was shown to form with its (x,t) trajectory comparing well to theoretical estimates. To characterise the microparticle, flow particle image velocimetry experiments were conducted at the nozzle exit, using particle payloads with varying diameter (2.7–48 μm), density (600–16,800 kg/m³) and mass (0.25–10 mg). The resultant microparticle velocities were temporally uniform. The experiments also show that the starting process does not significantly influence the microparticle nozzle exit velocities. The velocity distribution across the nozzle exit was also uniform for the majority of microparticle types tested. For payload masses typically used in pre-clinical drug and vaccine applications (≤ 1 mg), it was demonstrated that payload scaling does not affect the microparticle exit velocities. These characteristics show that the microparticle exit conditions are well controlled and are in agreement with ideal theory. These features combined with an attention to the practical requirements of a pre-clinical system make the device suitable for investigating microparticle penetration into the skin for drug delivery.