Fast RP-HPLC Method for the Determination of Bisoprolol.

Aim: To develop and validate a fast, robust, isocratic reversed-phase high performance liquid chromatographic method for the determination of bisoprolol in bulk and pharmaceutical formulations. Material and Method: Optimum separation of bisoprolol was achieved using as stationary phase a Zorbax SB-C18 column (100×3 mm; 5µm). The mobile phase was a mixture of phosphate buffer (pH = 3.5) and acetonitrile (70:30) with a flow rate of 1mL/min. The UV detection was performed at 225nm. The temperature of the column and autosampler was 25°C. The specificity was assessed by using metoprolol as internal standard. The method was validated in accordance with the current ICH guidelines in terms of linearity, limit of detection, limit of quantification, precision, accuracy, recovery and system suitability. Results: The retention time for bisoprolol was 1.158 minute. The calibration graph was linear in the concentration range 5-90 µg/mL. The LOD and LOQ of bisoprolol were 1.63 µg/mL and 4.94 µg/mL, respectively. The intra and interday precision of measurements were lower than the accepted criteria (RSD ≤ 2%). The recovery values of HPLC determination of bisoprolol from tablets proved that none of the excipients influenced the results of the analysis. Conclusions: The assay it was found to be accurate, reproducible, sensitive and less time consuming. The proposed method can be successfully applied to quality control studies of pharmaceutical products.

A NEW SPECTROPHOTOMETRIC METHOD FOR THE ASSAY OF LISINOPRIL.

AIM: A new spectrophotometric method for the assay of lisinopril using 2,4-dinitrophenol as reagent is described. MATERIAL AND METHODS: The method involved the addition of 2,4-dinitrophenol to lisinopril in methanol followed by absorbance measurement at 400 nm. Experimental conditions that provide wide linear range, maximum sensitivity, selectivity, accuracy and precisions were optimized. RESULTS AND DISCUSSIONS: Beer's law was obeyed in the concentration range 2.0-14.0 µg/mL. Linear regression equation of calibration graph was A = 0.005 + 0.045 x concentration, with a regression coefficient (r) of 0.9995 (n = 8). The limits of detection (LOD) and quantification (LOQ) calculated according to the ICH guidelines were 0.42 and 1.42 µg/mL, respectively. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different lisinopril concentrations; the intra-day and inter-day RSD was < 1.43% and accuracy was better than 1.72%. CONCLUSIONS: The proposed method is simple, easy to perform, sensitive, linear, precise, accurate and robust.

ANTINFLAMMATORY ACTIVITY OF AN N, N'-DISALICYLIDENEMETHYLENDIAMINE-DERIVED SCHIFF BIS BASE AND ITS COPPER(II) COMPLEX.

AIM: The cooper(II) complex combination of N, N'-disalicylidenemethylenediamine and the Schiff bis base were investigated for anti-inflammatory activity. MATERIAL AND METHODS: In vivo, the anti-inflammatory activity of the metallic complex in comparison with the activity of the Schiff bis base was tested by the method of Winter and co-workers using the Levy technique. RESULTS AND DISCUSSIONS: Our study on the anti-inflammatory activity of a new Schiff bis base and its complex cooper(II) combination showed that the Schiff bis bases exhibited significant anti-inflammatory action in acute experimental inflammation when compared to the control group. The copper cation from the complex combination enhanced the anti-inflammatory effect of the Schiff bis base, the effect being stronger at doses of 10 mg/kg cooper(II) complex. CONCLUSIONS: The Schiff bis base and its cooper(II) complex had an anti-inflammatory effect comparable to that of indomethacin.

Spectrophotometric method for estimation of bisoprolol fumarate in tablets.

UNLABELLED: Bisoprolol fumarate is prescribed for the treatment of hypertension and angina pectoris. AIM: The purpose of this study was to develop a simple, sensitive, accurate, and reproducible method for estimation of bisoprolol fumarate in tablets. MATERIAL AND METHODS: The proposed method was based on a yellow colored complex formed with tropaeolin 00, extractable in dichloromethane with maximum absorbance at 412 nm. The method was validated statistically. RESULTS: The linearity domain was observed in the concentration of 5-30 microg/ml. The recovery studies confirmed the accuracy of the proposed method. CONCLUSIONS: The proposed method can be applied for the routine analysis of bisoprolol from formulations.

Validation of a spectrophotometric assay method for bisoprolol using picric acid.

UNLABELLED: Bisoprolol is a drug belonging to beta blockers drugs used primarily for the treatment of cardiovascular diseases. AIM: A spectrophotometric method for quantitative determination of bisoprolol was developed based on the formation of a complex combination between bisoprolol and picric acid. MATERIAL AND METHODS: The complex combination of bisoprolol and picric acid has a maximum absorbance peak at 420 nm. Optimum working conditions were established and the method was validated. RESULTS: The method presented a good linearity in the concentration range 5-120 microg/ml (regression coefficient r2 = 0.9992). The RSD for the precision of the method was 1.74 and for the intermediate precision 1.43, and recovery values ranged between 98.25-101.48%. CONCLUSIONS: The proposed and validated spectrophotometric method for the determination of bisoprolol is simple and cost effective.

Pressure-induced colossal piezoresistance effect and the collapse of the polaronic state in the bilayer manganite (La(0.4)Pr(0.6))(1.2)Sr(1.8)Mn2O7.

We have investigated the effect of hydrostatic pressure as a function of temperature on the resistivity of a single crystal of the bilayer manganite (La(0.4)Pr(0.6))(1.2)Sr(1.8)Mn(2)O(7). Whereas a strong insulating behaviour is observed at all temperatures at ambient pressure, a clear transition into a metallic-like behaviour is induced when the sample is subjected to a pressure (P) of ~1.0 GPa at T < 70 K. A huge negative piezoresistance ~10(6) in the low temperature region at moderate pressures is observed. When the pressure is increased further (5.5 GPa), the high temperature polaronic state disappears and a metallic behaviour is observed. The insulator to metal transition temperature exponentially increases with pressure and the distinct peak in the resistivity that is observed at 1.0 GPa almost vanishes for P > 7.0 GPa. A modification in the orbital occupation of the e(g) electron between 3d(x(2)-y(2)) and 3d(z(2)-r(2)) states, as proposed earlier, leading to a ferromagnetic double-exchange phenomenon, can qualitatively account for our data.

Electronic confinement and ordering instabilities in colossal magnetoresistive bilayer manganites.

We present angle-resolved photoemission studies of (La{1-z}Pr{z}){2-2x}Sr{1+2x}Mn{2}O{7} with x=0.4 and z=0.1, 0.2, and 0.4 along with density functional theory calculations and x-ray scattering data. Our results show that the bilayer splitting in the ferromagnetic metallic phase of these materials is small, if not completely absent. The charge carriers are therefore confined to a single MnO{2} layer, which in turn results in a strongly nested Fermi surface. In addition to this, the spectral function also displays clear signatures of an electronic ordering instability well below the Fermi level. The increase of the corresponding interaction strength with z and its magnitude of ∼400 meV make the coupling to a bare phonon highly unlikely. Instead we conclude that fluctuating order, involving electronic and lattice degrees of freedom, causes the observed renormalization of the spectral features.

Spectrometric method for the assay of ramipril using molybdophosphoric acid.

UNLABELLED: Ramipril is a drug of the angiotensin converting enzyme inhibitor class. AIM: A new molecular absorbance spectrometric method was developed for the assay of ramipril using molybdophosphoric acid in acidic medium. MATERIAL AND METHODS: The reaction product showed a maximum absorbance at 361 nm. The optimum conditions of the reaction were established. The developed method was validated. RESULTS: The method showed a good linearity in the range of 8 - 36 microg/ml (correlation coefficient r = 0.9996). The detection limit (LD) was 0.86microg/ml and the quantification limit (LQ) 2.88 pg/ml. Precision and accuracy were determined (RSD = 1.15%); mean recovery was 98.90% in the 97.13-101.03% concentration range. CONCLUSIONS: The proposed method is simple, easy to perform, sensitive, linear, precise, accurate and robust.

The zero-field glassy ground state and field-induced ferromagnetic transition in (La0.4Pr0.6)1.2Sr1.8Mn2O7.

We have investigated glassy magnetic freezing in(La0.4Pr0.6)1.2Sr1.8Mn2O7 single crystals together with the field-induced transition to a metastable ferromagnetic phase using ac magnetic susceptibility and heat capacity measurements. The magnetization measurements show evidence for the development of a zero-field glassy ground state below 45 K along with a hysteretic, field-induced change in susceptibility associated with the transition to the ferromagnetic phase above 5 T. The heat capacity develops a clear peak at higher temperatures with the application of large magnetic fields, consistent with the development of a ferromagnetic order, while at low temperatures the Sommerfeld coefficient is monotonically reduced by an applied field, suggesting suppression of spin fluctuations. The heat capacity shows hysteretic behaviour, accompanied by a sharp decrease at a critical field, when held at fixed temperature, which does not recover on reducing the field back to zero. These measurements suggest that the zero-field ground state for (La0.4Pr0.6)1.2Sr1.8Mn2O7 consists of frozen disordered spin clusters, which develop into a metastable ferromagnetic state in modest magnetic fields.

[Construction and characterisation of a selective membrane electrode for the assay of lisinopril]. / Constructia si caracterizarea unui electrod membrana selectiv pentru determinarea lisinoprilului.

UNLABELLED: In order to analyze lisinopril using a selective membrane electrode, the electro-active compound was obtained and included in the selective membrane. The new analysis method was developed and validated. MATERIAL AND METHOD: The electro-active compound was obtained through the precipitation of lisinopril in acidic media using silicowolframic acid solution. The membrane was obtained by mixing the electro-active compound with polyvinylchloride using tetrahydrofurane as solvent. The solution was evaporated in order to obtain a thick membrane, which was then attached at one end of a polyvinylchloride tube. The internal Ag/AgCl reference electrode was inserted in that tube. The assembly was filled with a lisinopril internal solution. The electrode was characterized by establishing the following characteristics: electrode slope, selectivity, optimal pH range, response time and life-time period. The developed method was validated. RESULTS: The method showed a good linearity in the range of 10(-7) and 10(-2)M (the correlation coefficient r = 0.9991). The detection limit (LD) was 8,66 x 10(-8)M and the quantification limit (LQ) was 7,8 x 10(-7)M. There were established the precision (RSD = 1.73%) and the accuracy (mean recovery was 99.92%) CONCLUSIONS: The experimental results demonstrated a good sensibility.

Observation of phonons with resonant inelastic x-ray scattering.

Phonons, the quantum mechanical representation of lattice vibrations, and their coupling to the electronic degrees of freedom are important for understanding thermal and electric properties of materials. For the first time, phonons have been measured using resonant inelastic x-ray scattering (RIXS) across the Cu K-edge in cupric oxide (CuO). Analyzing these spectra using an ultra-short core-hole lifetime approximation and exact diagonalization techniques, we can explain the essential inelastic features. The relative spectral intensities are related to the electron-phonon coupling strengths.

Evaluation of some pharmaceutical formulations of lisinopril through dissolution testing.

AIM: Lisinopril is a drug of the angiotensin converting enzyme (ACE) inhibitor class that is primarily used in treatment of hypertension, congestive heart failure, heart attacks and also in preventing renal and retinal complications of diabetes. We compared the dissolution profiles of Lisinopril 20 mg tablets (Antibiotice S.A. lasi) and Zestril 20 mg tablets (Astra Zeneca). MATERIAL AND METHOD: Because lisinopril is a third class active substance, we performed dissolution tests in standard media at three pH values: 1.2, 4.5 and 6.8 using the paddle apparatus at 75 rpm. RESULTS: Both pharmaceutical formulations present a dissolution percentage more than 85% (Q) of the labeled amount. CONCLUSION: Both pharmaceutical formulations present similar dissolution profile. Key words:

[High blood and urine concentration of hepatotoxic mycotoxins (aflatoxin B1, sterigmatocystin) in patients with liver cirrhosis]. / Detectarea micotoxinelor hepatotoxice la pacienti cu ciroza Hepatica.

UNLABELLED: Aflatoxins and sterigmatocystin are potent carcinogens, certainly involved in pathogenesis of liver cancer. AIM: To evaluate the risk of mycotoxin intake and to determine the presence of aflatoxin B1 (AFB1) and sterigmatocystin (STC) in patients with liver cirrhosis. MATERIAL AND METHOD: The study included 92 patients (33 controls, 59 liver cirrhosis) that completed a food frequency questionnaire (FFQ). Blood and urine samples were collected and mycotoxins determined by high performance liquid chromatography. RESULTS: 18.18% samples in controls and 72.88% in cirrhosis group presented detectable levels of mycotoxins. The mean values of AFB1 in blood were 0.7 ng/mL in controls and 1.67 ng/mL in test group (p = 0.11); STC presented 60 times higher levels in second group (p < 0.01). AFB1 presented a mean level of 1.2 ng/mL in urine of test group (not detected in controls); STC presented 256 time higher concentration in urine of cirrhotic patients, with a perfect correlation between blood and urine levels in control (r=1) and no correlation in test group (r = 0.05). There were no correlations between mycotoxin, liver enzymes, alpha-fetoprotein and mycotoxin intake risk estimated by FFQ. CONCLUSION: Most of the patients presented detectable levels of mycotoxins, significantly increased in cases with liver cirrhosis, probable due to a specific metabolic pattern.

Effect of pressure on lattice distortion, transport and magnetic properties of Pr-substituted La(1.2)Sr(1.8)Mn(2)O(7) bilayered manganite.

We have studied the effect of pressure on the anomalous lattice striction, both in the ab-plane and along the c-axis, of (La,Pr)(1.2)Sr(1.8)Mn(2)O(7) single crystals over the temperature region where the paramagnetic insulator to ferromagnetic metal transition takes place. We have examined the temperature dependence of the resistivity and the magnetization under applied pressure. The chemical pressure effect due to Pr-substitution at the La site suppresses the transition temperature of the parent crystal, while the application of external pressure on Pr-substituted crystals enhances the double exchange driven metallic state, resulting in a stable rise of T(c).

[Analytical application of phosphotungstic acid complexes. Fabrication and characterisation of membrane selective electrodes for some H2 antihistaminics]. / Complecsi ai acidului fosfowolframic cu aplicatii analitice. Constructia si caracterizarea unor electrozi membrana selectivi pentru unele antihistaminice H2.

PVC matrix membrane selective electrodes for ranitidine, nizatidine and famotidine, based on sparingly soluble complexes, were prepared and characterized. The optimum functional pH range, response time, selectivity and lifetime were determined for each of the built electrodes. The linear range, precision and accuracy of each method were obtained by statistical interpretation of experimental results, while the limit of detection and thelimit of quantification were determined by a graphical method. All these electrodes were applied for the direct quantitative potentiometric determination of ranitidine hydrochloride, nizatidine and famotidine in pharmaceutical formulations.

[Analytical application of phosphotungstic acid complexes. Synthesis and characterisation]. / Complecsi ai acidului fosfowolframic cu aplicatii analitice. Sinteza si caracterizare.

UNLABELLED: Phosphotungstic acid forms salt type ionic association complexes with a large number of medicinal drugs that contain cation forming proton acceptor moieties. MATERIAL AND METHOD: Ranitidine, nizatidine and famotidine complexes with phosphotungstic acid were synthesized and subsequently characterized by their melting point, water solubility, specific absorbance, UV spectra and IR spectra. RESULTS: These sparingly soluble complexes were applied for the fabrication of membrane selective electrodes for quantitative potentiometric determination of ranitidine, nizatidine and famotidine. CONCLUSIONS: There have been synthesized phosphotungstic acid complexes with uses in fabrication of membrane selective electrodes for quantitative potentiometric determination of ranitidine, nizatidine and famotidine.

Steplike lattice deformation of single crystalline (La0.4Pr0.6)1.2Sr1.8Mn2O7 bilayered manganite.

We report a steplike lattice transformation of single crystalline (La0.4Pr0.6)1.2Sr1.8Mn2O7 bilayered manganite accompanied by both magnetization and magnetoresistive jumps, and examine the ultrasharp nature of the field-induced first-order transition from a paramagnetic insulator to a ferromagnetic metal phase accompanied by a huge decrease in resistance. Our findings support that the abrupt magnetostriction is closely related to an orbital frustration existing in the inhomogeneous paramagnetic insulating phase rather than a martensitic scenario between competing two phases.

[Quantitative determination of adrenaline by visible spectrophotometric method]. / Determinarea spectrofotometrica în vizibil a adrenalinei.

UNLABELLED: A sensible and rapid spectrophotometric assay for adrenaline was developed. MATERIAL AND METHOD: The method is based on the reaction with ammonium molybdate and sodium nitrite in acid medium. RESULTS: The obtained compound is stable, soluble in water and has the absorbtion maximum at 405 nm. Beer's law is valid within a concentration range of 20-160 microg/mL. The validity of the method was tested by statistical analysis of the experimental data using the linearity, the scale's calibration factor, the detection limit, the quantification limit and the precision. CONCLUSIONS: A new method for the assay of adrenaline in pharmaceutical products has been developed.

[Turbidimetric assay of famotidine]. / Determinarea cantitativa turbidimetrica a famotidinei sub forma de fosfomolibdat.

This paper proposes a new method for the quantitative determination of famotidine, based on its reaction with phosphomolybdic acid. The measurements were carried out at wavelength of 400 nm. This method has been validated and it has been applied to the determination of famotidine in pharmaceutical products.

[UV spectrophotometric assay of famotidine in combination with picrolonic acid, picrolinate]. / Determinarea cantitativa spectrofotometrica in uv a famotidinei sub forma de picrolonat.

Famotidine, belonging to H2-antagonist group, is a compound containing a thiazolic moiety and it is used in peptic ulcer therapy. This paper debates the possibility of developing a new ultraviolet spectrophotometric assessment by using the reaction between famotidine and picrolonic acid. We carried out our determinations at 362 nm, where the absorbency of famotidine - picrolonic acid complex is maximal, and we have established the optimal reaction conditions. This method was successfully applied for famotidine assay from pharmaceutical dosage forms.