LC-API/MS in Drug Metabolism and Pharmacokinetic Studies

The use of API interfaces with quadrupole mass spectrometers has been shown to give rise to good sensitivity, selectivity, and robustness for the interfacing of LC to MS. Since their introduction in the 1990s the technique has rapidly become widespread, but at the outset of this research programme, there were still a number of problems associated with it, particularly when dealing with complex sample matrices. The aim of this research programme was to study illustrative examples of the kinds of problems associated with the analysis of biological samples using LC-API-MS in an attempt to arrive at strategies which could be employed to eliminate, or at least compensate for, the problems. Commonly reported problems include the occurrence of matrix effects - a change in response of the target analyte(s) as a result of the presence in the samples of co /late eluting interferences. An investigation which compared ESI with APCI ionisation illustrated a significant drawback in the accepted methodology for the elimination of matrix effects. Optimal LC conditions for a number of assays may use non-MS-friendly mobile phases. A simple and convenient solution to this problem was found to be the post column addition of organic modifier, which reproducibly and reliably enhanced sensitivity. This approach was initially used for a range of dihydropyridine calcium channel blockers and was subsequently applied to a range of chiral compounds from different therapeutic groups to illustrate that this was applicable as a generic technique for increasing sensitivity (typically by around an order of magnitude) in low organic mobile phases. Strategies to develop and validate methods for the determination of endogenous analytes in a biological fluid were investigated. This involved the use of a surrogate matrix, to develop a method for the determination of endogenous testosterone in human serum and the use of non-matrix calibration standards for the successful development and validation of a method for the analysis of indolyl 3 acryloylglycine (IAG) in human urine. As a result of observations suggesting promotion of ionisation of deltamethrin in liver tissue sample extracts, it was postulated that this was due to the presence of high concentrations of surfactants. After confirming the effect, a series of systematic investigations were performed to attempt to understand the mechanism to be able to utilise this as a general method for the enhancement of signal with low sensitivity analytes. It was found that the type of surfactant and concentration used was directly associated with an increased (or decreased) response. Although there remain a number of problems associated with the use of LC-API-MS, the work undertaken for this thesis has successfully demonstrated a number of techniques that can be applied to overcome these problems. Knowledge of the nature of the sample undergoing analysis, the required analytical conditions, and where required careful application of one of the techniques described will ensure that a robust method can be readily developed

Electrically tunable selective reflection of light from ultraviolet to visible and infrared by heliconical cholesterics

Cholesteric liquid crystals with helicoidal molecular architecture are known for their ability to selectively reflect light with the wavelength that is determined by the periodicity of molecular orientations. Here we demonstrate that by using a cholesteric with oblique helicoidal(heliconical) structure, as opposed to the classic right-angle helicoid, one can vary the wavelength of selectively reflected light in a broad spectral range, from ultraviolet to visible and infrared (360-1520 nm for the same chemical composition) by simply adjusting the electric field applied parallel to the helicoidal axis. The effect exists in a wide temperature range (including the room temperatures) and thus can enable many applications that require dynamically controlled transmission and reflection of electromagnetic waves, from energy-saving smart windows to tunable organic lasers, reflective color display, and transparent see-through displays.Comment: 11 pages, 5figure

Time-constrained scenario-based practical examinations (TSPEs) – an alternative to OSCEs?

Assessing clinical competence in medical professionals typically involves both work-based assessment and simulated clinical examinations. Student veterinary nurses are assessed through the Nursing Progress Log during placement, then by means of practical examinations – objective structured clinical examinations (OSCEs). Time-constrained scenario-based practical examinations (TSPEs) are adapted from traditional OSCEs, including assessment of similar practical skills, but by means of a single patient scenario. This article introduces the theory behind using TSPEs and covers practical considerations for course teams considering adopting this assessment style

Nematic twist-bend phase with nanoscale modulation of molecular orientation

A state of matter in which molecules show a long-range orientational order and no positional order is called a nematic liquid crystal. The best known and most widely used (for example, in modern displays) is the uniaxial nematic, with the rod-like molecules aligned along a single axis, called the director. When the molecules are chiral, the director twists in space, drawing a right-angle helicoid and remaining perpendicular to the helix axis; the structure is called a chiral nematic. Here using transmission electron and optical microscopy, we experimentally demonstrate a new nematic order, formed by achiral molecules, in which the director follows an oblique helicoid, maintaining a constant oblique angle with the helix axis and experiencing twist and bend. The oblique helicoids have a nanoscale pitch. The new twist-bend nematic represents a structural link between the uniaxial nematic (no tilt) and a chiral nematic (helicoids with right-angle tilt)

Nematic Twist-Bend Phase with Nanoscale Modulation of Molecular Orientation

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Understanding the remarkable difference in liquid crystal behaviour between secondary and tertiary amides : the synthesis and characterisation of new benzanilide-based liquid crystal dimers

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Hydrogen bonding and the design of twist-bend nematogens

Acknowledgements The work was supported by the National Science Centre (Poland) under the grant no. 2016/22/A/ST5/00319. RW gratefully thanks the Carnegie Trust for the Universities of Scotland for the award of a PhD Scholarship (2015-2018). The Erasmus programme is thanked for supporting a study visit for CAC to Warsaw. Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author statement Rebecca Walker: Investigation, Formal analysis, Validation, Visualisation, Writing – Original Draft, Writing – Reviewing and Editing Damian Pociecha: Visualisation, Investigation, Formal analysis Catriona Crawford: Investigation, Formal analysis John MD Storey: Resources, Supervision Ewa Gorecka: Investigation, Formal analysis, Resources, Supervision Corrie T Imrie: Conceptualization, Supervision, Resources, Writing – Reviewing and EditingPeer reviewedPostprin

Critical behavior of the optical birefringence at the nematic to twist bend nematic phase transition

This research was supported by the National Science Centre (Poland) under the grant no. 2016/22/A/ST5/00319. NV acknowledges the support of the Slovenian Research Agency (ARRS), through the research programme P1-0055.Peer reviewedPublisher PD