Development of a rapid,multi-class method for the confirmatory analysis of anti-inflammatory drugs in bovine milk using liquid chromatography tandem mass spectrometry

A rapid liquid chromatography tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the simultaneous identification, confirmation and quantitation of seven licensed anti-inflammatory drugs (AIDs) in bovine milk. The method was validated in accordance with the criteria defined in Commission Decision 2002/657/EC. Two classes of AIDs were investigated, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). The developed method is capable of detecting and confirming dexamethasone (DXM), betamethasone (BTM), prednisolone (PRED), tolfenamic acid (TLF), 5-hydroxy flunixin (5-OH-FLU), meloxicam (MLX) and 4-methyl amino antipyrine (4-MAA) at their associated maximum residue limits (MRLs). These compounds represent all the corticosteroids and NSAIDs licensed for use in bovine animals producing milk for human consumption. These compounds have never been analysed before in the same method and also 4-methyl amino antipyrine has never been analysed with the other licensed NSAIDs. The method can be considered rapid as permits the analysis of up to 30 samples in one day. Milk samples are extracted with acetonitrile; sodium chloride is added to aid partition of the milk and acetonitrile mixture. The acetonitrile extract is then subjected to liquid–liquid purification by the addition of hexane. The purified extract is finally evaporated to dryness and reconstituted in a water/acetonitrile mixture and determination is carried out by LC–MS/MS. Decision limit (CCα) values and detection capability (CCβ) values have been established for each compound.     

On the approximation of nonlinear singular self-adjoint second order boundary value problems

We investigate the approximation of the solutions of a class of nonlinear second order singular boundary value problems with a self-adjoint linear part. Our strategy involves two ingredients. First, we take advantage of certain boundary condition functions to obtain well behaved functions of the solutions. Second, we integrate the problem over an interval that avoids the singularity. We are able to prove a uniform convergence result for the approximate solutions. We describe how the approximation is constructed for the various values of the deficiency index associated with the differential equation. The solution of the nonlinear problem is obtained by a globally convergent iterative method.     

Existence and location results for sign-changing solutions for three-point boundary value problems using Leray-Schauder degree

In this paper, by using the modification function technique and the Leray-Schauder degree method some existence and multiplicity results for sign- changing solutions of certain three-point boundary value problems are obtained. The main result of this paper is an improvement on a former existence result for sign-changing solutions of certain three-point boundary value problems.     

Existence and location results for sign-changing solutions for three-point boundary value problems using Leray-Schauder degree

In this paper, by using the modification function technique and the Leray-Schauder degree method some existence and multiplicity results for sign- changing solutions of certain three-point boundary value problems are obtained. The main result of this paper is an improvement on a former existence result for sign-changing solutions of certain three-point boundary value problems.     

Constant-sign solutions for systems of singular integral equations of Hammerstein type

We consider the system of Hammerstein integral equations

where T>0 is fixed, ρ_i’s are given functions and the nonlinearities f_i(t,x₁,x₂,…,x_n) can be singular at t=0 and x_j=0 where j{1,2,,n}. Criteria are offered for the existence of constant-sign solutions, i.e., θ_iu_i(t)≥0 for t[0,T] and 1≤i≤n, where θ_i{1,−1} is fixed. The tools used are a nonlinear alternative of Leray–Schauder type, Krasnosel’skii’s fixed point theorem in a cone and Schauder’s fixed point theorem. We also include examples and applications to illustrate the usefulness of the results obtained.     

Determination of association constants of inclusion complexes of steroid hormones and cyclodextrins from their electrophoretic mobility

CE estimation of the association constants of several steroid hormones with beta-CD and gamma-CD and their hydroxypropyl derivative is presented. Estriol, 17beta-estradiol, ethynylestradiol, estrone, progesterone, mestranol and norethindrone are among the target analytes. The calculation of the cyclodextrin:analyte association constants were performed from the electrophoretic mobility values of steroids at different concentration of CDs in the run buffer. The reliability of the final data was ensured by employing three different linearisation plots (double reciprocal fit, Y-reciprocal fit and X-reciprocal fit). The highest inclusion affinity of target analytes was observed towards gamma-CD and its hydroxypropyl derivative, which is demonstrated by high association constant values and corresponding good linearity of the plots. The affinity of steroids towards a particular CD type based on physical and structural characteristics is explored.     

Backlighter development at the National Ignition Facility (NIF): Zinc to zirconium

K-shell X-ray emission from laser-irradiated planar Zn, Ge, Br, and Zr foils was measured at the National Ignition Facility for laser irradiances in the range of 0.6–9.5 × 10¹⁵ W/cm². The incident laser power had a pre-pulse to enhance the laser-to-X-ray conversion efficiency (CE) of a 2–5 ns constant-intensity pulse used as the main laser drive. The measured CE into the 8–16 keV energy band ranged from 0.43% to 2%, while the measured CE into the He-like resonance 1s2–1s2p(1P) and intercombination 1s2–1s2p(3P) transitions, as well as from their 1s2(2s,2p)l–1s2p(2s,2p)l satellite transitions for l = 1, 2, 3, corresponding to the Li-, Be-, and B-like resonances, respectively, ranged from 0.3% to 1.5%. Absolute and relative CE measurements are consistent with X-ray energy scaling of (hν)^?3 to (hν)^?5, where hν is the X-ray energy. The temporal evolution of the broadband X-ray power was similar to the main laser drive for ablation plasmas having a critical density surface.     

Determination of imatinib and its active metabolite N-desmethyl imatinib in human plasma by liquid chromatography/tandem mass spectrometry

Imatinib is a first-line treatment for chronic myelogenous leukaemia (CML). The pharmacokinetics of imatinib in patients with CML are characterised by large interpatient variability. Concentration monitoring of imatinib and its active metabolite N-desmethyl imatinib (DMI) is considered necessary to enhance the safe and effective use of imatinib. A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry assay was developed for the simultaneous determination of imatinib and its metabolite DMI in human plasma. After proteins were precipitated with acetonitrile, imatinib, DMI and the internal standard D8-imatinib were resolved on a Gemini-NX 3?μm C18 column using gradient elution of 0.05?% formic acid and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves of imatinib and DMI were adequately fitted by quadratic equations (r?>?0.999) over the concentration range of 10 to 2,000?ng/mL which encompasses clinical concentrations. Bias was ≤±8.3?%, intra- and inter-day coefficients of variation (imprecision) were ≤8.0?% and the limit of quantification was 10?ng/mL for both imatinib and DMI. The assay is being used successfully in clinical practice to enhance the safe and effective use of imatinib.     

Viscosity approximation methods for pseudo-contractive semigroups in Banach spaces

We study the strong convergence of two viscosity iteration processes for pseudo-contractive semigroup and for ?$?$-strongly pseudo-contractive mapping in uniformly convex Banach spaces with uniformly Gâteaux differentiable norm. As special cases, we get strong convergence of two viscosity iteration processes for approximating common fixed points of nonexpansive semigroups in certain Banach spaces. The results presented in this paper extend and generalize previous results.     

Low loss propagation in slow light photonic crystal waveguides at group indices up to 60

We have designed slow light photonic crystal waveguides operating in a low loss and constant dispersion window of Δλ = 2 nm around λ = 1565 nm with a group index of n_g = 60. We experimentally demonstrate a relatively low propagation loss, of 130 dB/cm, for waveguides up to 800 μm in length. This result is particularly remarkable given that the waveguides were written on an electron-beam lithography tool with a writefield of 100 μm that exhibits stitching errors of typically 10–50 nm. We reduced the impact of these stitching errors by introducing “slow–fast–slow” mode conversion interfaces and show that these interfaces reduce the loss from 320 dB/cm to 130 dB/cm at n_g = 60. This significant improvement highlights the importance of the slow–fast–slow method and shows that high performance slow light waveguides can be realised with lengths much longer than the writing field of a given e-beam lithography tool.