Utility of certain nucleophilic aromatic substitution reactions for the assay of pregabalin in capsules

<p>Abstract</p> <p>Background</p> <p>Pregabalin (PG) is an anticonvulsant, analgesic and anxiolytic drug. A survey of the literature reveals that all the reported spectrophotometric methods are either don't offer high sensitivity, need tedious extraction procedures, recommend the measurement of absorbance in the near UV region where interference most probably occurs and/or use non specific reagent that don't offer suitable linearity range.</p> <p>Results</p> <p>Two new sensitive and simple spectrophotometric methods were developed for determination of pregabalin (PG) in capsules. Method (I) is based on the reaction of PG with 1,2-naphthoquinone-4-sulphonate sodium (NQS), yielding an orange colored product that was measured at 473 nm. Method (II) is based on the reaction of the drug with 2,4-dinitrofluorobenzene (DNFB) producing a yellow product measured at 373 nm. The different experimental parameters affecting the development and stability of the reaction product in methods (I) and (II) were carefully studied and optimized. The absorbance-concentration plots were rectilinear over the concentration ranges of 2-25 and 0.5-8 μg mL^-1for methods (I) and (II) respectively. The lower detection limits (LOD) were 0.15 and 0.13 μg mL^-1and the lower quantitation limits (LOQ) were 0.46 and 0.4 μg mL^-1for methods (I) and (II) respectively.</p> <p>Conclusion</p> <p>The developed methods were successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recoveries of PG in its capsule were 99.11 ± 0.98 and 100.11 ± 1.2 (n = 3). Statistical analysis of the results revealed good agreement with those given by the comparison method. Proposals of the reaction pathways were postulated.</p

Multiwavelength observations of a VHE gamma-ray flare from PKS 1510-089 in 2015

Context. PKS 1510 089 is one of only a few flat spectrum radio quasars detected in the very-high-energy (VHE, > 100 GeV) gamma-ray band.Aims. We study the broadband spectral and temporal properties of the PKS 1510 089 emission during a high gamma-ray state.Methods. We performed VHE gamma-ray observations of PKS 1510 089 with the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescopes during a long, high gamma-ray state in May 2015. In order to perform broadband modeling of the source, we have also gathered contemporaneous multiwavelength data in radio, IR, optical photometry and polarization, UV, X-ray, and GeV gamma-ray ranges. We construct a broadband spectral energy distribution (SED) in two periods, selected according to VHE gamma-ray state.Results. PKS 1510 089 was detected by MAGIC during a few day-long observations performed in the middle of a long, high optical and gamma-ray state, showing for the first time a significant VHE gamma-ray variability. Similarly to the optical and gamma-ray high state of the source detected in 2012, it was accompanied by a rotation of the optical polarization angle and the emission of a new jet component observed in radio. However, owing to large uncertainty on the knot separation time, the association with the VHE gamma-ray emission cannot be firmly established. The spectral shape in the VHE band during the flare is similar to those obtained during previous measurements of the source. The observed flux variability sets constraints for the first time on the size of the region from which VHE gamma rays are emitted. We model the broadband SED in the framework of the external Compton scenario and discuss the possible emission site in view of multiwavelength data and alternative emission models

Multi-wavelength characterization of the blazar S5~0716+714 during an unprecedented outburst phase

The BL Lac object S5~0716+714, a highly variable blazar, underwent an impressive outburst in January 2015 (Phase A), followed by minor activity in February (Phase B). The MAGIC observations were triggered by the optical flux observed in Phase A, corresponding to the brightest ever reported state of the source in the R-band. The comprehensive dataset collected is investigated in order to shed light on the mechanism of the broadband emission. Multi-wavelength light curves have been studied together with the broadband Spectral Energy Distributions (SEDs). The data set collected spans from radio, optical photometry and polarimetry, X-ray, high-energy (HE, 0.1 GeV 100 GeV) with MAGIC. The flaring state of Phase A was detected in all the energy bands, providing for the first time a multi-wavelength sample of simultaneous data from the radio band to the VHE. In the constructed SED the \textit{Swift}-XRT+\textit{NuSTAR} data constrain the transition between the synchrotron and inverse Compton components very accurately, while the second peak is constrained from 0.1~GeV to 600~GeV by \textit{Fermi}+MAGIC data. The broadband SED cannot be described with a one-zone synchrotron self-Compton model as it severely underestimates the optical flux in order to reproduce the X-ray to $\gamma$-ray data. Instead we use a two-zone model. The EVPA shows an unprecedented fast rotation. An estimation of the redshift of the source by combined HE and VHE data provides a value of $z = 0.31 \pm 0.02_{stats} \pm 0.05_{sys}$, confirming the literature value. The data show the VHE emission originating in the entrance and exit of a superluminal knot in and out a recollimation shock in the inner jet. A shock-shock interaction in the jet seems responsible for the observed flares and EVPA swing. This scenario is also consistent with the SED modelling

Multi-wavelength characterization of the blazar S5 0716+714 during an unprecedented outburst phase

Context. The BL Lac object S5 0716+714, a highly variable blazar, underwent an impressive outburst in January 2015 (Phase A), followed by minor activity in February (Phase B). The MAGIC observations were triggered by the optical flux observed in Phase A, corresponding to the brightest ever reported state of the source in the R-band.Aims.The comprehensive dataset collected is investigated in order to shed light on the mechanism of the broadband emission.Methods. Multi-wavelength light curves have been studied together with the broadband spectral energy distributions (SEDs). The sample includes data from Effelsberg, OVRO, Metsahovi, VLBI, CARMA, IRAM, SMA, Swift-UVOT, KVA, Tuorla, Steward, RINGO3, KANATA, AZT-8+ST7, Perkins, LX-200, Swift-XRT, NuSTAR, Fermi-LAT and MAGIC.Results. The flaring state of Phase A was detected in all the energy bands, providing for the first time a multi-wavelength sample of simultaneous data from the radio band to the very-high-energy (VHE, E> 100 GeV). In the constructed SED, the Swift-XRT +NuSTAR data constrain the transition between the synchrotron and inverse Compton components very accurately, while the second peak is constrained from 0.1 GeV to 600 GeV by Fermi+MAGIC data. The broadband SED cannot be described with a one-zone synchrotron self-Compton model as it severely underestimates the optical flux in order to reproduce the X-ray to y-ray data. Instead we use a two-zone model. The electric vector position angle (EVPA) shows an unprecedented fast rotation. An estimation of the redshift of the source by combined high-energy (HE, 0.1 GeV < E < 100 GeV) and VHE data provides a value of ,z = 0.31 +/- 0.02(stats) +/- 0.05(sys), confirming the literature value.Conclusions. The data show the VHE emission originating in the entrance and exit of a superluminal knot in and out of a recollimation shock in the inner jet. A shock-shock interaction in the jet seems responsible for the observed flares and EVPA swing. This scenario is also consistent with the SED modeling

Monitoring of the radio galaxy M 87 during a low -emission state from m 2012 to 2015 with MAGIC

M 87 is one of the closest (z = 0.004 36) extragalactic sources emitting at very high energies (VHF, E > 100 GeV). The aim of this work is to locale the region of the VHF gamma-ray emission and to describe the observed broad-band spectral energy distribution (SED) during the low VHF gamma-ray state. The data from M 87 collected between 2012 and 2015 as part of a MAGIC monitoring programme are analysed and combined with multiwavelength data from Fermi-LAT, Chandra, HST, FVN, VLBA, and the Liverpool Telescope. The averaged VHE gamma-ray spectrum can be fitted from 100 GeV to 10 TeV with a simple power law with a photon index of (-2.41 0.07), while the integral flux above 300 GeV is (1.44 0.13) x 10-12 cm 2 s I. During the campaign between 2012 and 2015, M87 is generally found in a low-emission state at all observed wavelengths. The VIIE gamma-ray flux from the present 2012-2015M 87 campaign is consistent with a constant flux with some hint of variability ( 3 a) on a daily time-scale in 2013. The low-state gamma-ray emission likely originates from the same region as the flare-state emission. Given the broad-band SED, both a leptonic synchrotron self-Compton and a hybrid photohadronic model reproduce the available data well, even if the latter is preferred. We note, however, that the energy stored in the magnetic field in the leptonic scenario is very low, suggesting a matter-dominated emission region

MAGIC and Fermi-LAT gamma-ray results on unassociated HAWC sources

The HAWC Collaboration released the 2HWC catalogue of TeV sources, in which 19 show no association with any known high-energy (HE; E greater than or similar to 10 GeV) or very-high-energy (VHE; E greater than or similar to 300 GeV) sources. This catalogue motivated follow-up studies by both the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) and Fermi-LAT (Large Area Telescope) observatories with the aim of investigating gamma-ray emission over a broad energy band. In this paper, we report the results from the first joint work between High Altitude Water Cherenkov (HAWC), MAGIC, and Fermi-LAT on three unassociated HAWC sources: 2HWC J2006+341, 2HWC J1907+084*, and 2HWC J1852+013*. Although no significant detection was found in the HE and VHE regimes, this investigation shows that a minimum 1 degrees extension (at 95 per cent confidence level) and harder spectrum in the GeV than the one extrapolated from HAWC results are required in the case of 2HWC J1852+013*, whilst a simply minimum extension of 0.16 degrees (at 95 per cent confidence level) can already explain the scenario proposed by HAWC for the remaining sources. Moreover, the hypothesis that these sources are pulsar wind nebulae is also investigated in detail

VERY HIGH ENERGY gamma-RAYS FROM THE UNIVERSE'S MIDDLE AGE: DETECTION OF THE z=0.940 BLAZAR PKS 1441+25 WITH MAGIC

The flat-spectrum radio quasar PKS 1441+25 at a redshift of z = 0.940 is detected between 40 and 250 GeV with a significance of 25.5 sigma using the MAGIC telescopes. Together with the gravitationally lensed blazar QSO. B0218 +357 (z = 0.944), PKS. 1441+25 is the most distant very high energy (VHE) blazar detected to date. The observations were triggered by an outburst in 2015 April seen at GeV energies with the Large Area Telescope on board Fermi. Multi-wavelength observations suggest a subdivision of the high state into two distinct flux states. In the band covered by MAGIC, the variability timescale is estimated to be 6.4 +/- 1.9 days. Modeling the broadband spectral energy distribution with an external Compton model, the location of the emitting region is understood as originating in the jet outside the broad-line region (BLR) during the period of high activity, while being partially within the BLR during the period of low (typical) activity. The observed VHE spectrum during the highest activity is used to probe the extragalactic background light at an unprecedented distance scale for ground-based gamma-ray astronomy