Enhanced spectrofluorimetric determination of the multitargeted tyrosine kinase inhibitor, crizotinib, in human plasma via micelle-mediated approach

Purpose: To quantify the multi-targeted tyrosine kinase inhibitor, crizotinib, in human plasma and bulk powder by highly sensitive micellar enhanced spectrofluorimetric procedure.Method: The developed procedure was based on measuring the fluorescence intensity of crizotinib (CRZ) in sodium dodecyl sulphate (SDS) micellar system at 404 nm after excitation at 271 nm. Validation of the developed procedure was carried out following ICH (International Council for Harmonization) guidelines.Results: Maximum fluorescence intensity (FI) was attained by addition of 0.2 mL SDS and 0.2 mL HCl (1N) to CRZ aliquots and then dilution with distilled water. There was a linear relationship between the FI of CRZ and its concentration over the range, 5 – 400 ng/mL, with limit of detection and of quantification of 1.857 and 5.628 ng/mL respectively. The developed procedure was successfully applied to assay CRZ in pure powder form and spiked human plasma with mean recovery of 100.68 ± 0.37 and 99.98 ± 0.20 %, respectively.Conclusion: The developed procedure is simple and sensitive, and can be applied to routine analysis of CRZ in pure powder form as well as in clinical laboratories for the determination of CRZ in plasma.Keywords: Crizotinib, Spectrofluorimetry, Micelle, Human plasma, Sodium dodecyl sulphat

A new spectrofluorimetric assay method for vandetanib in tablets, plasma and urine

Purpose: To develop a simple and sensitive spectrofluorimetric method for the determination of vandetanib (VDB) in tablets (containing 100 mg of the drug) and biological fluids (spiked human plasma and urine).Methods: The proposed method is based on examining the intrinsic fluorescence intensity of VDB in acetonitrile at 480 nm after excitation at 330 nm. Factors affecting fluorescence intensity of the cited drug (VDB), including the influence of pH, diluting solvent and time, were studied and optimized by one factor at a time approach. A calibration curve was constructed by plotting VDB fluorescence intensity at 480 nm versus VDB concentrations in ng mL-1. The method was validated according to the recommendations of International Conference on Harmonisation (ICH) for validation of the analytical proceduresResults: The linearity range of the method was 20 – 600 ng mL-1, with limits of quantification (LOQ) and of detection (LOD) of 30.45 and 10.05 ng mL-1, respectively. The adopted method was applied successfully to the quantitation of VDB in pure powder form (100.90 ± 0.91 %), laboratory prepared tablets (97.86 ± 1.42 %), spiked human plasma (97.97 ± 2.36 %) and urine (97.59 ± 0.87 %). Comparison of the proposed method with that of liquid chromatography-tandem mass spectrometry showed that there was no significant difference (p < 0.05) between the two methods in terms of accuracy and precision.Conclusion: The proposed method is simple and highly sensitive and, consequently, can be applied to assay VDB in biological samples as well as in dosage form.Keywords: Vandetanib, Spectrofluorimetry, Assay, Validation, Human plasma, Human urine, Dosage form

Polarization observables of the gamma d --> PiNN reaction in the Delta(1232)-resonance region

Polarization observables of the three charge states of the pion for the $\gamma d\to\pi NN$ reaction with polarized photon beam and/or oriented deuteron target are evaluated over the whole $\Delta$(1232)-resonance region adopting a nonrelativistic model based on time-ordered perturbation theory. Results for the $\pi$-meson spectra, linear photon asymmetry, vector and tensor target asymmetries are presented. Particular attention is given, for the first time, to double polarization asymmetries for which we present results for $T_{20}^{\ell}$ and $T_{2\pm 2}^{\ell}$. We found that all other double polarization asymmetries of photon and deuteron target are vanished.Comment: 17 Pages, 8 Figures, accepted for publication in Int. J. Mod. Phys.

Sense of Belonging: International Student Enrollment in Business Programs

Objective: The authors sought to develop a better understanding of the sense of belonging to international students enrolled in graduate-level business programs. Background: A theoretical framework exists to support the sense of belonging as a significant predictor of academic persistence. However, a paucity of literature exists that investigates international students’ sense of belonging in graduate-level programs.Method: The qualitative case-study research method was used to collect data via semi-structured focus groups and interviews with 13 participants. Data were recorded, transcribed, themed, and coded to establish research findings.Results: Participants reported barriers such as loneliness, isolation, immobility, and language barriers in the development of academic and social belonging.Conclusion: Campus-based support services focus on integrating international students into the campus community. However, little effort is placed on helping domestic students support the sense of belonging to their international peers. Furthermore, there is some evidence indicating that international students either failed to engage or were unaware of services that might help them overcome social and academic barriers. Application: Educational institutions should improve the ease of access, enhance existing, and develop additional services to help improve the sense of belonging to international students

Sense of Belonging: International Student Enrollment in Business Programs

Objective: The authors sought to develop a better understanding of the sense of belonging to international students enrolled in graduate-level business programs. Background: A theoretical framework exists to support the sense of belonging as a significant predictor of academic persistence. However, a paucity of literature exists that investigates international students’ sense of belonging in graduate-level programs.Method: The qualitative case-study research method was used to collect data via semi-structured focus groups and interviews with 13 participants. Data were recorded, transcribed, themed, and coded to establish research findings.Results: Participants reported barriers such as loneliness, isolation, immobility, and language barriers in the development of academic and social belonging.Conclusion: Campus-based support services focus on integrating international students into the campus community. However, little effort is placed on helping domestic students support the sense of belonging to their international peers. Furthermore, there is some evidence indicating that international students either failed to engage or were unaware of services that might help them overcome social and academic barriers. Application: Educational institutions should improve the ease of access, enhance existing, and develop additional services to help improve the sense of belonging to international students

Simultaneous quantitative analysis of olmesartan, amlodipine and hydrochlorothiazide in their combined dosage form utilizing classical and alternating least squares based chemometric methods

Simultaneous spectrophotometric analysis of a multi-component dosage form of olmesartan, amlodipine and hydrochlorothiazide used for the treatment of hypertension has been carried out using various chemometric methods. Multivariate calibration methods include classical least squares (CLS) executed by net analyte processing (NAP-CLS), orthogonal signal correction (OSC-CLS) and direct orthogonal signal correction (DOSC-CLS) in addition to multivariate curve resolution-alternating least squares (MCR-ALS). Results demonstrated the efficiency of the proposed methods as quantitative tools of analysis as well as their qualitative capability. The three analytes were determined precisely using the aforementioned methods in an external data set and in a dosage form after optimization of experimental conditions. Finally, the efficiency of the models was validated via comparison with the partial least squares (PLS) method in terms of accuracy and precision

A novel method to determine new potent angiotensin inhibitor, azilsartan, in human plasma via micelle-enhanced spectrofluorimetry using cremophor RH 40

Purpose: To develop a micelle-enhanced spectrofluorimetric method for the assay of azilsartan (AZL) in bulk form and spiked human plasma without the need for derivatization procedure.Method: The proposed method was based on studying the fluorescence behavior of AZL in Cremophor RH 40 (Cr RH 40) micellar system. The fluorescence intensity was measured at 371 nm after excitation at 264 nm. The proposed procedure was validated according to International Council on Harmonization (ICH) guidelines.Results: In aqueous solution, the fluorescence intensity of AZL was greatly enhanced by more than 3- fold in the presence of Cr RH 40. The fluorescence –concentration plot was linear over the range of 10 – 500 ng.mL-1, with a limit of detection of 3.287 ngmL-1. The proposed method was successfully applied to the determination of AZL in pure powder form and spiked human plasma. The mean recovery of AZL in spiked human plasma using the proposed method was 90.54 ± 1.17 %.Conclusion: The suggested method is highly sensitive and simple, and can easily be applied for the quantification of AZL in pure powder form as well as in biological fluids such as plasmaKeywords: Azilsartan, Spectrofluorimetry, Spiked human plasma, Micellar syste

Liquid chromatographic-tandem mass spectrometric assay for simultaneous quantitation of tofacitinib, cabozantinib and afatinib in human plasma and urine

Purpose: To develop a simple, adequately sensitive, and practical liquid chromatographic-mass spectrometric method to simultaneously quantify three tyrosine kinase inhibitors, viz, tofacitinib (TOF), cabozantinib (CBZ) and afatinib (AFB) after their extraction from both human plasma and urine.Methods: Blood and urine samples were obtained from healthy volunteers who admitted to not being on any medications. The investigated analytes were chromatographically separated on a C18 column (Luna®-PFP 100Å column, 50 mm × 2.0 mm i.d., 3.0 μm) with the aid of a mobile phase containing A; acetonitrile (ACN) and B; 0.01 M ammonium formate buffer (pH 4.1) pumped at a rate of 0.3 mL.min-1 in the ratio A:B, 50:50 v/v. Analyte monitoring was achieved by tandem mass spectrometry interfaced with an electrospray ionization source with the aid of multiple reaction monitoring (MRM) mode for analytes quantification.Results: The proposed method permitted a specific and sensitive determination of the investigated TKIs in the linear range of 1.0 - 100 ng mL-1 with correlation coefficient (r2) of 0.9991, 0.9997, and 0.9998 for TOF, CBZ and AFB, respectively. The method was validated with regard to its limits of quantification (ranging from 0.91 to 1.24 ng mL-1 for the 3 analytes), intra- and inter assay accuracy (in the range -1.85 to 1.22 %) and precision (0.71 - 5.12 %). The method was also validated in terms of recovery from both studied matrices, robustness and matrix effect.Conclusion: The results obtained reveal that the developed method is simple, specific and highly efficient for routine determination of the studied analytes in human plasma and urine. It can be reliably applied for high throughput analysis of clinical samples containing the investigated analytes.Keywords: Tyrosine kinase inhibitors, Tofacitinib, Cabozantinib, Afatinib, LC-MS/MS, human plasm

Operation and control design of an input-series-input-parallel-output-series conversion scheme for offshore DC wind systems

High-power converters for high-voltage direct current transmission systems and collecting networks are attracting increasing interest for application in large offshore wind farms. Offshore wind farms are capable of generating more electric energy at lower cost when compared with onshore wind systems. In this study, DC/DC voltage conversion should be achieved with a power converter that uses readily available semiconductor devices. A modular DC/DC converter can achieve the required system currents and voltages without exceeding semiconductor ratings. In this study, the operation and control strategy for an input-series–input-parallel–output-series (ISIPOS) energy conversion system for wind systems are presented. The ISIPOS system allows the direct connection of wind turbines to the DC grid. In this research, the design process to control the input and output currents and voltages is explained. In addition, a new method to ensure voltage and current sharing between the different modules is presented and explained. The basic structure, control design, and system performance are tested using MATLAB/SIMULINK. Practical results validate the control design flexibility of the ISIPOS topology when controlled by a TMSF280335 DSP

Non-Bloch-Siegert-type power-induced shift of two-photon electron paramagnetic resonances of charge-carrier spin states in an OLED

We present Floquet theory-based predictions and electrically detected magnetic resonance (EDMR) experiments scrutinizing the nature of two-photon magnetic resonance shifts of charge-carrier spin states in the perdeuterated $\pi$-conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene] (d-MEH-PPV) under strong magnetic resonant drive conditions (radiation amplitude $B_1$ ~ Zeeman field $B_0$). Numerical calculations show that the two-photon resonance shift with power is nearly drive-helicity independent. This is in contrast to the one-photon Bloch-Siegert shift that only occurs under non-circularly polarized strong drive conditions. We therefore treated the Floquet Hamiltonian analytically under arbitrary amplitudes of the co- and counter-rotating components of the radiation field to gain insight into the nature of the helicity dependence of multi-photon resonance shifts. In addition, we tested Floquet-theory predictions experimentally by comparing one-photon and two-photon charge-carrier spin resonance shifts observed through room-temperature EDMR experiments on d-MEH-PPV-based bipolar injection devices [i.e., organic light emitting diode structures (OLEDs)]. We found that under the experimental conditions of strong, linearly polarized drive, our observations consistently agree with theory, irrespective of the magnitude of $B_1$, and therefore underscore the robustness of Floquet theory in predicting nonlinear magnetic resonance behaviors.Comment: 22 pages, 5 figure