Quantitative estimation of riluzole in human plasma by LC-ESI-MS/MS and its application to a bioequivalence study

A novel simple, sensitive, selective, and rapid high-performance liquid chromatography coupled with tandem mass spectrometry method was developed and validated for quantification of riluzole in human plasma. The chromatography was performed by using a Zorbax-SB-C18 (4.6 × 75 mm, 3.5 μm) column , isocratic mobile phase 0.1% formic acid/acetonitrile (10:90 v/v), and an isotope-labeled internal standard (IS), [¹³C,¹⁵N₂]riluzole. The extraction of drug and internal standard was performed by liquid–liquid extraction and analyzed by MS in the multiple reaction monitoring (MRM) mode using the respective [M+H]⁺ ions, m/z 235.0/165.9 for riluzole and m/z 238.1/169.0 for the IS. The calibration curve was linear over the concentration range 0.5–500.0 ng/ml for riluzole in human plasma. The limit of quantification (LOQ) was demonstrated at 0.5 ng/ml. The within-batch and between-batch precision were 0.6–2.3% and 1.4–5.7%, and accuracy was 97.1–101.1% and 98.8–101.2% for riluzole respectively. Drug and IS were eluted within 3.0 min. The validated method was successfully applied in a bioequivalence study of riluzole in human plasma.     

Low frequency electromagnetic waves in a multi-ion plasma

The dispersion characteristics of low-frequency electromagnetic waves are studied in a plasma containing hydrogen ions and positively and negatively charged oxygen ions and electrons. This composition of the plasma approximates very well the coma of comet Halley where many heavy ions have been observed in appreciable numbers. The excitation of these waves results from the relative motion between the protons and the heavy ions, which are considered unmagnetised and, therefore, may act like a beam. We find that the wave growth increases with increasing heavy ion densities, beam velocities and propagation angles.     

Fast and Slow Mode Solitary Waves in a Five-Component Plasma

We have investigated fast- and slow-mode solitary profiles in a five-component plasma consisting of positively and negatively charged pair ions, hydrogen ions, and hotter and colder electrons. Of these, the heavier ions and colder photoelectrons are of cometary origin while the other components are of solar origin; the electrons are described by kappa distributions. The Zakharov-Kuznetsov (ZK) equation is derived, and solutions for fast- and slow-mode solitary structures are plotted for parameters relevant to comet Halley. We found that the presence of hydrogen ions determines the polarity of the fast- and slow-mode solitary structures. Also, variations of equilibrium number density of hydrogen ions and charge numbers on the heavier pair ions act differently on the fast- and slow-mode solitary structures. The addition of hydrogen ions significantly affects the amplitude of the solitary structures for the fast mode. Further, the cyclotron frequency of the lighter and heavier ions has a noticeable effect on the width of the solitary waves.     

Visible-light mediated trifluoromethylation of p-quinone methides by 1,6-conjugate addition using pyrylium salt as organic photocatalyst

A transition metal free visible light mediated organo photoredox catalyzed trifluoromethylation of p-quinone methides (p-QMs) to construct fluoro-analogs of dichlorodiphenyltrichloroethane (DDT) is reported using a bench stable, inexpensive Langlois reagent as a trifluoromethyl radical source. This protocol could generate a benzylic C(sp³)-CF₃ bond with excellent yield under mild reaction conditions using 1,6-conjugate addition/aromatization of trifluoromethyl radical in the absence of any external additives. Further, we demonstrate di-trifluoromethylation and gram scale synthesis of this reaction.     

Propagation of the electromagnetic ion-cyclotron wave in a fusion plasma

The propagation of the electromagnetic ion-cyclotron wave in a fusion plasma described by a loss-cone structure is discussed. The wavelength is assumed to be much larger than the ion Larmour radius and the ion plasma frequency ≫ the ion-cyclotron frequency. The two modes that propagate in the plasma interact strongly and fuse together under certain conditions making the plasma unstable. The coalescence of the modes is found to decrease with an increase in electron temperature.     

Stability of electrostatic ion cyclotron waves in a multi-ion plasma

We have studied the stability of the electrostatic ion cyclotron wave in a plasma consisting of isotropic hydrogen ions (H⁺) and temperature-anisotropic positively (O⁺) and negatively (O⁻) charged oxygen ions, with the electrons drifting parallel to the magnetic field. Analytical expressions have been derived for the frequency and growth/damping rate of ion cyclotron waves around the first harmonic of both hydrogen and oxygen ion gyrofrequencies. We find that the frequencies and growth/damping rates are dependent on the densities and temperatures of all species of ions. A detailed numerical study, for parameters relevant to comet Halley, shows that the growth rate is dependent on the magnitude of the frequency. The ion cyclotron waves are driven by the electron drift parallel to the magnetic field; the temperature anisotropy of the oxygen ions only slightly enhance the growth rates for small values of temperature anisotropies. A simple explanation, in terms of wave exponentiation times, is offered for the absence of electrostatic ion cyclotron waves in the multi-ion plasma of comet Halley.     

Near perpendicular propagation of ion cyclotron modes in a deuterium-hydrogen-oxygen fusion plasma

A dispersion relation for the near perpendicular propagation of the electromagnetic ion cyclotron wave has been derived in a fusion plasma that has deuterium as a majority species, hydrogen as a minority species and fully ionized oxygen as an impurity constituent; all being modelled by loss cone distribution functions. The wave has a frequencyω around the deuterium ion gyrofrequency-Ω_D and a wavelength much longer than its Larmor radiusγ _LD(k _⊥ γ _LD<1); the plasma itself being characterized by large ion plasma frequencies (ω _PD ² >Ω _D ² ). Two modes, a low frequency (LF) and a high frequency (HF) mode of opposite electrical energy can propagate in the plasma; the instabilities that arise are thus due to an interaction of modes of opposite energies. We find that while hydrogen tends to destabilize the plasma, the impurity oxygen ions have the reverse effect. Also the plasma is most stable when the ratios of the perpendicular components of oxygen-to-deuterium and hydrogen-to-deuterium temperatures are kept low. Detailed studies of the wave propagation characteristics and energy reveal the close resemblance of a loss cone plasma containing oxygen to a stable Maxwellian plasma in regard to wave stability, propagation and energy.     

Determination of Rizatriptan in Human Plasma by Liquid Chromatography Stable Isotope Dilution Electrospray MS�CMS for Application in Bioequivalence Study

A simple, sensitive, selective, rapid, rugged, reproducible and specific liquid chromatography?Ctandem mass spectrometry (LC?CMS/MS) method was used for quantitative estimation of rizatriptan (RZ) in human plasma using rizatriptan-d ₆ (RZD6) as internal standard (IS). Chromatographic separation was performed on Ascentis Express RP Amide C18, 50 × 4.6 mm, 2.7 ??m column with isocratic mobile phase composed of 10 mM ammonium formate:acetonitrile (20:80 v/v) at flow rate of 0.5 mL min^?1. RZ and RZD6 were detected with proton adducts at m/z (amu) 270.2 ?? 201.2 and 276.1 ?? 207.1, respectively, in multiple reaction monitoring (MRM) positive mode. Liquid?Cliquid extraction was used and validated over a linear concentration range of 0.1?C100.0 ng mL^?1 with correlation coefficient r ² ?? 0.9981. The limit of quantification (LOQ) and limit of detection (LOD) were found to be 0.1 ng mL^?1 and 12.5 fg, respectively. Intra- and inter-day precision were within 1.7?C3.1% and 2.8?C3.7%, and accuracy within 96.0?C101.7% and 99.7?C101.4% for RZ. Drug was found to be stable throughout three freeze?Cthaw cycles. The method was successfully employed for analysis of plasma samples following oral administration of RZ (10 mg) in 25 healthy Indian male human volunteers under fasting conditions.     

Ion cyclotron instabilities in a mildly relativistic hydrogen-deuterium fusion plasma

A dispersion relation for the perpendicular propagation of the electromagnetic ion cyclotron wave around the second harmonic of the deuterium ion gyrofrequency in a mildly relativistic, anisotropic Maxwellian plasma with hydrogen as the majority species and deuterium as the minority component has been derived. The work has been carried out in the frame of reference of the majority hydrogen ions; to these ions the waves at 2Θ_D would be at its own gyrofrequency. Using a small quantityɛ to order all relevant parameters of the plasma, it was possible to derive the dispersion relations in a simple form. To the lowest order the relativistic factors do not enter the dispersion relation. The plasma can now support two modes—one above and the other below the hydrogen gyrofrequency in agreement with the assumptions. This was also verified numerically using a standard root solver thereby justifying the correctness of the ordering scheme. In the next higher order, the dispersion relation is a quartic equation and is sensitively dependent on the relativistic factors. The plasma can now support four modes, both above and below the hydrogen gyrofrequency and consistent with the ordering scheme used. However the modes can now coalesce resulting in complex conjugate roots to the dispersion relation thereby indicating an instability. The advantage of such a scheme is that two dispersion relations — one of which is independent of the relativistic factors and the other which is sensitively dependent on them can be separated out.     

Stability of second harmonic minority heating in magnetic mirror systems

A dispersion relation has been derived to study the stability of ion cyclotron (IC) propagation at the second harmonic of the minority component deuterium in a mirror confined plasma that has hydrogen as the majority species. We have worked in the frame of the majority ions; our dispersion relation can thus be used to study IC propagation in a single ion plasma also. Analysis of the dispersion relation yields two modes — one below and the other above the ion gyro-frequency Θ_H of hydrogen. The expression for the growth rate is used to explicitly show that an instability can arise in the plasma when the loss-cone indexj⩾3; this instability being a result of the coalescing of the two modes supported by the plasma. Unfortunately, the minority component deuterium does not decrease this instability and thus the proposed scheme of IC heating at the second harmonic of the minority component seems unsuited to mirror devices.