The Development and Validation of a Stability-Indicating UHPLC-DAD Method for Determination of Perindopril l-Arginine in Bulk Substance and Pharmaceutical Dosage Form

A stability-indicating ultra-high-performance liquid chromatography (UHPLC) method with a diode array detector was developed and validated for the determination of cis/trans isomers of perindopril l-arginine in bulk substance and pharmaceutical dosage form. The separation was achieved on a Poroshell 120 Hilic (4.6 × 150 mm, 2.7 µm) column using a mobile phase composed of acetonitrile–0.1 % formic acid (20:80 v/v) at a flow rate of 1 mL min^?1. The injection volume was 5.0 µL and the wavelength of detection was controlled at 230 nm. The selectivity of the UHPLC-DAD method was confirmed by determining perindopril l-arginine in the presence of degradation products formed during acid–base hydrolysis and oxidation as well as degradation in the solid state, at an increased relative air humidity and in dry air. The method’s linearity was investigated in the ranges 0.40–1.40 µg mL^?1 for isomer I and 0.40–2.40 µg mL^?1 for isomer II of perindopril l-arginine. The UHPLC-DAD method met the precision and accuracy criteria for the determination of the isomers of perindopril l-arginine. The limits of detection and quantitation were 0.1503 and 0.4555 µg mL^?1 for isomer I and 0.0356 and 0.1078 µg mL^?1 for isomer II, respectively.     

An Approach to Transfer Methods from HPLC to UHPLC Techniques in Some Carbapenems

Stability-indicating LC methods were developed and validated for the quantitative determination of doripenem, meropenem and tebipenem in the presence of their degradation products formed during forced degradation studies. Isocratic HPLC and UHPLC separations were performed with a core–shell Kinetex 1.7, 2.6 and 5 µm, all C18, 100A, 100 × 2.1 mm columns and the mobile phase composed of acetonitrile and 12 mmol L⁻¹ ammonium acetate in different ratios. The flow rates of the mobile phase were: 0.5 mL min⁻¹ for 1.7 µm column, and 1.0 mL min⁻¹ for 2.6 and 5 µm ones. Detection wavelength was 298 nm and temperature was set at 30 °C. All analysed drugs were exposed to stress conditions which caused their hydrolysis and thermal degradation. The methods were validated by evaluation of linearity, accuracy, precision, selectivity and robustness. Proposed methods were successfully applied for the determination of investigated antibiotics during kinetic studies in aqueous solutions and in the solid state. The advantages of chromatographic procedures which are based on the use of C18 stationary phases with different particle sizes in the analysis of selected carbapenems were discussed.

     

Liquid chromatography tandem mass spectrometry with ion trap and triple quadrupole analyzers for determination of thyreostatic drugs in urine and muscle tissue

Liquid chromatography tandem mass spectrometry methods were developed and validated to screen for and confirm residues of the thyreostatic drugs: tapazole, thiouracil, methylthiouracil, propylthiouracil, and phenylthiouracil in bovine and porcine urine and muscle tissues using dimethylthiouracil as internal standard. Thyreostats were extracted from urine samples with diethyl ether after derivatisation with 3-iodobenzylbromide in basic medium (pH 8.0) and analyzed by gradient elution on a Nucleosil C18 column with ion trap mass spectrometry detection using an electrospray source and triple quadrupole MS detection with turbo spray source. Thyreostats were extracted from muscle tissue with methanol, the denaturation of matrix protein was performed and then the same steps as for the urine samples were carried out. The methods were validated in accordance with the Commission Decision 2002/657/EC. Good thyreostats recoveries were obtained (from 82% to 117%) as well as acceptable within-lab reproducibility. The values of the decision limit CCα and the detection capability CCβ of five thyreostatic drugs are found to be below the recommended concentration set at 10 μg L(-1) (kg(-1)). The results of the validation demonstrate that liquid chromatography mass spectrometry with ion trap detection does not meet the criteria for confirmation for some thyreostats and therefore was applied for screening purpose only.     

The effect of lipid oxidation on the water permeability of phospholipids bilayers

The effect of lipid oxidation on water permeability of phosphatidylcholine membranes was investigated by means of both scattering stopped flow experiments and atomistic molecular dynamics simulations. Formation of water pores followed by a significant enhancement of water permeability was observed. The molecules of oxidized phospholipids facilitate pore formation and subsequently stabilize water in the membrane interior. A wide range of oxidation ratios, from 15 to 100 mol%, was considered. The degree of oxidation was found to strongly influence the time needed for the opening of a pore. In simulations, the oxidation ratio of 75 mol% was found to be a threshold for spontaneous pore formation in the tens of nanosecond timescale, whereas 15 mol% of oxidation led to significant water permeation in the timescale of seconds. Once a pore was formed, the water permeability was found to be virtually independent of the oxidation ratio.     

Zonal Jet Creation from Secondary Instability of Drift Waves for Plasma Edge Turbulence

A new strategy is presented to explain the creation and persistence of zonal flows widely observed in plasma edge turbulence. The core physics in the edge regime of the magnetic-fusion tokamaks can be described qualitatively by the one-state modified Hasegawa-Mima (MHM for short) model, which creates enhanced zonal flows and more physically relevant features in comparison with the familiar Charney-Hasegawa-Mima (CHM for short) model for both plasma and geophysical flows. The generation mechanism of zonal jets is displayed from the secondary instability analysis via nonlinear interactions with a background base state. Strong exponential growth in the zonal modes is induced due to a non-zonal drift wave base state in the MHM model, while stabilizing damping effect is shown with a zonal flow base state. Together with the selective decay effect from the dissipation, the secondary instability offers a complete characterization of the convergence process to the purely zonal structure. Direct numerical simulations with and without dissipation are carried out to confirm the instability theory. It shows clearly the emergence of a dominant zonal flow from pure non-zonal drift waves with small perturbation in the initial configuration. In comparison, the CHM model does not create instability in the zonal modes and usually converges to homogeneous turbulence.     

Remarks on the breakdown of smooth solutions for the 3-D Euler equations

The authors prove that the maximum norm of the vorticity controls the breakdown of smooth solutions of the 3-D Euler equations. In other words, if a solution of the Euler equations is initially smooth and loses its regularity at some later time, then the maximum vorticity necessarily grows without bound as the critical time approaches; equivalently, if the vorticity remains bounded, a smooth solution persists.Partially supported by O.N.R. Contract No. N00014-76-C-0316 and N.S.F. Grant No. MCS-81-01639Partially supported by N.S.F. Grant No. MCS-82-00171Partially supported by N.S.F. Grant No. MCS-81-02360     

Cathodic stripping determination of iron at a platinum electrode modified by adsorption of adenosine-5'-monophosphate

Irreversible adsorption of adenosine-5'-monophosphate onto platinum yields an electrode surface which is readily plated by formation of a non-labile complex with iron(III) present initially in solution or formed by oxidation of iron(II). A negative potential scan subsequent to a 60-s deposition step produces a cathodic stripping peak, the height of which is proportional to the sum of the Pe(III) and Fe(II) concentrations in solution. Oxalate can be used to mask the response to Fe(III). The method is shown to be applicable to determinations of Fe(III) and Fe(II) in the concentration range lO^-8–lO^-6 mol l^-1.     

A luminescence probe for measurements of electron-exchange rates in polymer films on electrodes

The effect of metal ions on the, reduction of 1,10-phenanthroline-5,6-quinone (1), 5,8-quinolinequinone (II) and 6,7-dichloro-5, 8-quinolinequinone (III) has been investigated in 50% dimethylsulfoxide+water solvent. 1 contains the 1,10-phenanthroline structure in both its quinone and hydroquinone forms, while II and III contain the 8-hydroxyquinoline structure in the hydroquinone forms. Complexation of the hydroquinones of II and III by metal ions causes positive shifts in the quinone half-wave potentials. These shifts have been used to calculate conditional formation constants for Pb²⁺(II) and Pb²⁺ and Zn²⁺(III). The quinone form of I binds strongly to Ni²⁺, Co²⁺ and Zn²⁺ but not to Ca²⁺. Mg²⁺. Mg₂₊. Mn²⁺ and Pb²⁺. With the latter four metals, binding to the hydroquinone from of I was detected and formation constants were determined. In addition to binding both the quinone and hydroquinone forms at the nitrogen atoms, Ni₂₊ Co²⁺ and Zn²⁺ formed complexes at the 1,2-dihydroxy site of the hydroquinone of I.     

The validity of nonlinear geometric optics for weak solutions of conservation laws

The method of weakly nonlinear geometric optics is one of the main formal perturbation techniques used in analyzing nonlinear wave motion for hyperbolic systems. The tacit assumption in using such perturbation methods is that the corresponding solutions of the hyperbolic system remain smooth; since shock waves typically form in such solutions, these assumptions are rarely satisfied in practice. Nevertheless, in a variety of applied contexts, these methods give qualitatively reliable answers for discontinuous weak solutions. Here we give a rigorous proof for the validity of nonlinear geometric optics for general weak solutions of systems of hyperbolic conservation laws in a single space variable. The methods of proof do not mimic the formal construction of weakly nonlinear asymptotics but instead rely on structural symmetries of the approximating equations, stability estimates for intermediate asymptotic times, and the rapid decay in variation of weak solutions for large asymptotic times.Partially supported by NSF Grant No. DMS-8301135Partially supported by NSF Grant No. MCS-81-02360 and ARO Grant No. 483964-25530