Determination of pKa values of 2-amino-2-oxazolines by capillary electrophoresis.

The dissociation constants of new 2-amino-2-oxazolines were determined by capillary electrophoresis (CE) as a new technique. A method based on a linear model has been used in the CE determination. A series of eight 2-amino-2-oxazolines are investigated to determine their ionization constant. Among them, three new oxazolines synthesized are presented. The Ka values were obtained from the plots of reciprocal effective mobility against inverse concentrations of protons. The potentiometric method (PM) was performed as a comparative method. No significant differences were observed between the determined dissociation constants using both methods. Thus, the pKa values have been found to vary between 8.55 and 8.68.

Separation of new antidepressants and their metabolites by micellar electrokinetic capillary chromatography.

Selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenergic reuptake inhibitors (SNaRIs) and noradrenergic and specific serotoninergic antidepressant (NaSSA) are widely used in the treatment of depression. An increase in antidepressant intoxications led to the development of reliable analytical methods for their analysis. A new determination procedure for these compounds (milnacipran, venlafaxine, desmethylvenlafaxine, mirtazapine, desmethylmirtazapine, citalopram, desmethylcitalopram, fluvoxamine, paroxetine, sertraline and fluoxetine) was developed by micellar electrokinetic capillary chromatography (MEKC) with diode array detection (DAD). Separation and determination were optimised on an uncoated fused-silica capillary (600 mm, 75 microm I.D.). The migration buffer consisted of 20 mM sodium borate, pH 8.55, with 20 mM SDS and 15% isopropanol, at an operating voltage of 25 kV. The column temperature was maintained at 40 degrees C. Injection in the capillary was performed in the hydrodynamic mode (0.5 p.s.i., 15 s). In these conditions, the migration time of the antidepressants was less than 11 min. In most cases, calibration curves were established for 30 - 2000 ng/ml (r > 0.995). The limit of detection and the limit of quantification were ranged between 10 and 20 and between 20 and 30 ng/ml, respectively, for all the molecules. This method allowed the determination of some of these compounds in biological fluids (blood, urine) in post-mortem cases. Samples (1 ml) were extracted with diethyl ether (5 ml) at pH 9.6 and reconstituted in diluted migration buffer. Similar results were obtained by a HPLC-DAD determination, performed as a reference method. These results suggest that this MEKC method can be useful for the determination of new antidepressants in post-mortem cases.

Spectrophotometric, spectrofluorimetric, HPLC and CZE determination of mirtazapine in pharmaceutical tablets.

Four analytical methods have been developed for the quality control of tablets containing mirtazapine: spectrophotometry, spectrofluorimetry, high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). All the methods only require a simple extraction procedure of mirtazapine from the tablets before analysis. The concentration of mirtazapine in solutions was determined in the linearity range of 5-25 microg/ml at lambda=315 nm for spectrophotometry and at lambda=220 nm for HPLC and CZE. Spectrofluorimetric determinations were achieved at lambda(excitation)=328 nm and lambda(emission)=415 nm in the linearity range of 2-25 ng/ml. All the methods gave similar results and were validated for selectivity, linearity, precision and sensitivity. Spectrometric methods gave slightly higher RSD values (up to 2.54%). The four methods were directly and easily applied to the pharmaceutical preparation with accuracy, resulting from recovery experiments between 99.72% in HPLC and 101.47% in spectrofluorimetry.

Comparison of high-performance liquid chromatography and capillary zone electrophoresis for the determination of parabens in a cosmetic product.

A high-performance liquid chromatographic method (HPLC) and a capillary zone electrophoresis method (CZE) have been developed for the analysis of methylparaben, ethylparaben, propylparaben and butylparaben in a commercial cosmetic product. A very simple extraction procedure with acidified diethylether was developed. The HPLC method involved a C18 reversed-phase column and a gradient of methanol and water-acetic acid (1%). Electrophoretic separation was performed on a fused-silica capillary with a mixed 15 mM tetraborate buffer (pH 9.2) and methanol (85:15, v/v). The calibration curves were linear from 1 to 40 microg/ml in HPLC and from 5 to 200 microg/ml in CZE. The limit of detection in CZE (0.21 microg/ml) was higher than in HPLC (0.05 microg/ml). Repeatability and intermediate precision were satisfactory for both methods (RSD values < 3.23% in HPLC and < 3.26%, in CZE). Only HPLC allowed the separation of butylparaben isomeric forms when CZE analysis was less time and reagents consuming. These results suggest that HPLC and CZE coupled with a simple extraction process are both suitable for parabens determination in cosmetic products.

Determination of urea, allantoin and lysine pyroglutamate in cosmetic samples by hydrophilic interaction chromatography.

A new HPLC method using a Polyhydroxyethyl A column involving hydrophilic interaction chromatography (HILIC) is described for the simultaneous determination of urea, allantoin and lysine pyroglutamate in a cosmetic cream. Validation of the method was accomplished with respect to linearity, repeatability and limits of detection/quantification. Compound recoveries approach 100% with acceptable RSD values. The method is very simple since no derivatisation is necessary. Furthermore, it allows the rapid and direct chromatographic analysis of urea and hence could provide an alternative to other methods used to determine this compound in biological or cosmetic samples.

Effect of cholera toxin on glutamine metabolism and transport in rabbit ileum.

The aim of the present study was to evaluate the effect of cholera toxin on energy balance from intestinal glutamine metabolism and oxidation, glutamine-dependent sodium absorption, and cholera toxin-dependent ion flux. Cholera toxin-stimulated sodium and L-glutamine ileal transport and metabolism were studied in Ussing chambers. Glutamine (10 mM) transport and metabolism were simultaneously studied using (14)C flux and HPLC. In the same tissues, the flux of each amino acid was studied by HPLC, and glutamine metabolism and oxidation were studied by the determination of amino acid specific activity and (14)CO(2) production. In control tissues, glutamine stimulated sodium absorption and was mainly oxidized. The transepithelial flux of intact glutamine represented 45% of glutamine flux across the luminal membrane. The other metabolites were glutamate and, to a lesser degree, citrulline, ornithine, and proline. Cholera toxin did not alter glutamine-stimulated sodium absorption, glutamine oxidation, transport, and metabolism. In conclusion, the present results indicate that cholera toxin does not alter glutamine intestinal function and metabolism. In addition, approximately 95% of the energy provided by glutamine oxidation remains available to the enterocyte.

Lipophilicity force field profile: an expressive visualization of the lipophilicity molecular potential gradient.

This paper proposes a new tool that allows us to see the following in the same frame: (1) 3D geometrical features of a molecule, and (2) pseudo-3D representation of the lipophilicity molecular potential. It thus becomes very easy to compare the lipophilicity molecular potential gradient of different molecules having the same pharmacological properties. An example of two structurally dissimilar anti-PAF molecules is given.

[Assay of plasma isosorbide dinitrate and its metabolites after oral administration of immediate and delayed-action forms]. / Dosage plasmatique du dinitrate d'isosorbide et de ses métabolites après administration orale de formes à libération immédiate ou prolongée.

This paper describes a kinetic comparative study of plasma concentrations of isosorbide dinitrate (ISDN) and its mononitrate derivatives (2-ISMN or 5-ISMN) after oral administration of a sustained release form of ISDN or a (non) sustained release form of 5-ISMN. The blood extracts determinations were performed by electron capture gas chromatography which is an accurate and sensitive method suitable for the quantitation of concentrations in the nanogram per ml range. The results are in good agreement with those of the literature. The standard form of 5-ISMN is rapidly absorbed. The Tmax value is approximately 1H with a corresponding Cmax value close to 400 ng/ml. For the sustained release drugs, the Tmax increases to 6H and Cmax is nearly half the 5-ISMN standard form value. Considering the administered dose, it seems better to use 5-ISMN than ISDN. For a long lasting treatment of angina pectoris and ischaemic cardiac diseases, both forms can be used.