[Patient information. Guidelines for practitioners - March 2000].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
H Fabre
Publications and source records attributed to H Fabre.
Robustness testing for a capillary electrophoresis method using the "short-end injection" technique.
A multivariate approach for testing the robustness of a capillary electrophoresis method using the "short-end injection" technique is presented. Firstly, a Plackett and Burman (PB) design with 11 factors (eight real factors and three dummies) was used to identify the critical factors on resolution, plate number, plate count, asymmetry and assay. Then, the factors which were found to be significant were studied in a central composite design to predict the variation of resolution inside the area investigated in the PB design. PB and central composite designs yielded conclusions that were in good agreement with one another. They showed that the separation could be considered as robust, notwithstanding the fact that some factors where found to be statistically significant and should be controlled (injected volume and electrolyte concentration). Using the factor values which gave the worst-case situation for Rs still led to acceptable values for this parameter.
Electrophoresis, Capillary↗
Determination of taurine in plasma by capillary zone electrophoresis following derivatisation with fluorescamine.
A novel capillary zone electrophoresis method is described for the determination of taurine in plasma. The method is rapidly executed and is highly selective for taurine as separation is based on the difference in ionisation of this amino acid from that of other amino acids. Following addition of homotaurine as internal standard, plasma proteins were precipitated with acetonitrile and the supernatant was derivatised with fluorescamine in the presence of a borate buffer. Capillary electrophoresis (CE) separations were carried out in reverse polarity mode at 27.5 kV on a Beckman P/ACE MDQ CE instrument, equipped with a diode array detector (DAD) set at 266 nm. The sample tray was cooled to 5 degrees C and separations were carried out at 20 degrees C. The fused-silica capillary was 50.2 cm in length (40.2 cm to detector) with an internal diameter of 75 microm. A capillary conditioning solution was applied daily in order to suppress the residual electroosmotic flow (EOF). The method, which was validated using feline plasma as the blank matrix, was shown to be linear and reproducible over the concentration range 2.5-100 microg/mL. The coefficients of variation (CVs) of replicate analyses were less than 4.5% at 1 microg/mL taurine in feline plasma and less than 3% for 2.5 microg/mL in human plasma. Recovery was estimated at 99.2% with a CV of 4.85%. It has been demonstrated that quantitation in aqueous solution yields similar results to those obtained by interpolation on a plasma calibration curve provided that subtraction for the taurine peak in unspiked plasma is carried out and that a suitable internal standard is employed.
Animals↗
Determination of homotaurine as impurity in calcium acamprosate by capillary zone electrophoresis.
A method is reported which allows the quantification of homotaurine as an impurity in the drug. After addition of taurine as an internal standard, the sample is derivatised with fluorescamine at ambient temperature in 10 mM borate buffer, pH 9.2. The analytes are separated by capillary zone electrophoresis in a 31.2 cm (21 cm to the detector) x 100 microns I.D. fused-silica capillary at a potential of +7 kV and 25 degrees C. A 40 mM borate buffer, pH 9.2, is used as the electrolyte and detection is carried out at 205 nm. The validation tests showed that the method is reliable between 0.01% and 0.15% (m/m) of homotaurine with respect to the active drug. The limits of quantitation (0.01%, m/m) and detection (0.004%, m/m) allows to control the homotaurine content of the drug substance for which the maximum tolerated level is 0.05% (m/m). The proposed procedure (derivatisation and separation) developed in CE is rapid (20-25 min) by comparison to that currently used in HPLC (75 min). Satisfactory agreement was found between several batches of acamprosate analysed by CE and HPLC.
Acamprosate↗
Column liquid chromatography determination of vitamins A and E in powdered milk and local flour: a validation procedure.
A high-performance liquid chromatography method was developed for the simultaneous routine determination of vitamins A and E in powdered milk and flour made from local plants and purchased from open markets in the Ivory Coast. The method involves saponification followed by extraction with a mixture of organic solvents. The vitamins were resolved by reversed-phase HPLC and detection at a single wavelength. The main tests of method validation were applied to the procedure. The results show the reliability of the analytical method for the intended application.
Animals↗
Evaluation of capillary zone electrophoresis and micellar electrokinetic capillary chromatography with direct injection of plasma for the determination of cefotaxime and its metabolite.
Quantitative aspects of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) were investigated for the determination of cefotaxime (C) and its deacetyl metabolite (DA) in human plasma in a concentration range of therapeutic interest. For CZE, plasma samples spiked with C and DA were injected after deproteinization with acetonitrile, and analytes were separated in a fused silica capillary using a borate buffer at pH 9.2 as electrolyte; no suitable internal standard was found. For MECC, plasma samples spiked with C, DA, and theobromine as internal standard were directly injected after dilution with water and analyzed using a phosphate buffer, pH 8.00, containing 165 mM SDS as separation electrolyte and a fused silica capillary. Both methods gave satisfactory interday precision with respect to migration times (RSD < 1%) and gave linear responses over the concentration ranges investigated (5-100 mg L-1 C and 5-20 mg L-1 DA). For CZE, intraday RSD (n = 4 graphs) between the slopes of the calibration graphs was acceptable (5.7%) for C. The corresponding figures for interday precision (n = 4 days) were fair (16.1%) in comparison to those obtained with MECC, for which the RSD was 1.49% when theobromine was used as internal standard. A satisfactory interday precision between slopes was also obtained with MECC even without the use of an internal standard (RSD = 4.38%), which demonstrated the ruggedness of this method. Detection limits (S/N = 3) were about 2 mg L-1 (CZE) and 1 mg L-1 in plasma (MECC) for C and DA. MECC was shown to be superior with regard to simplicity, rapidity, precision, and sensitivity.
Cefotaxime↗
Robustness testing in liquid chromatography and capillary electrophoresis.
The definition and objectives of robustness testing are given and the essential features of the methodology which can be applied using a multivariate approach in liquid chromatography and capillary electrophoresis are described. Guidelines are given for the different steps which are involved in using screening and response surface designs. It is shown that screening designs may be sufficient to set the method limits but that response surface designs are of major interest in method transfer because they give a comprehensive picture of the behaviour and limitations of the method.
Chromatography, High Pressure Liquid↗
[The lawyer's interpretation of the expert's report].
Explore the source record for details and available documents.
Expert Testimony↗
Electrochemical oxidation of CBS-113 A, a new anti-inflammatory drug: applicability to liquid chromatography-electrochemical detection.
The electrochemical properties of a new non-steroidal anti-inflammatory drug (2-hydroxy-4-methylphenyl-2-aminothiazole hydrochloride; CBS-113 A) have been studied using voltammetry in direct current and cyclic modes at glassy carbon disk electrodes. The results show an oxidative process with a diffusion-controlled and a reversible mechanism; these data agree with those obtained in a reversed-phase high-performance liquid chromatography (HPLC) system coupled either with amperometric (single glassy carbon electrode) or coulometric detection (two porous graphite electrodes in series) set at potentials of +0.65 V (vs. Ag/AgCl) and +0.4 V (vs. Pd/H2), respectively. Similar electrochemical properties were found for 2-hydroxyphenyl-2-amino-5'-methylthiazole hydrochloride (RD-1546) which is a potential internal standard. An HPLC system coupled with a UV detector (lambda = 272 nm) and an amperometric detector (+0.65 V) showed a gain in sensitivity of about 10 using electrochemical detection (ED) for the determination of CBS-113 A in human plasma. Linearity range, precision and accuracy were calculated and showed the potential application of HPLC-ED to pharmacokinetic studies of CBS-113 A in plasma.
Anti-Inflammatory Agents, Non-Steroidal↗
[The indispensable necessity for informed consent before voluntary female sterilization].
Explore the source record for details and available documents.
Documentation↗
[Voluntary female sterilization: legislation and jurisprudence in France].
Female sterilisation, widely used as a contraceptive technique in France for many decades, is now a cause for concern among clinicians in relation to the personal legal risks involved in such procedures. Questions concerning the position of insurers in relation to application of civil hability insurance in the context of these procedures and their possible complications reinforce this uncertainty. Sterilisation, in the absence of any therapeutic objective, which is at the centre of the current debate, can be considered to be a deliberate mutilation, performed as an illegal procedure and the insurer, on principle, cannot insure the consequences of such an intentionally concomitted act. As described in this paper, the absence of legislation concerning this procedure and the limited legal debate on this subject tend to perpetuate the ambiguity between what is prohibited by law, but largely tolerated in reality.
Female↗
[What are the medico-legal implications of induced labor?].
Explore the source record for details and available documents.
Female↗
Photoisomerization kinetics of cefuroxime axetil and related compounds.
The photoisomerization kinetics of aqueous solutions of cefuroxime axetil under irradiation at 254 nm was investigated by HPLC. The overall degradation is the result of a competition between the isomerization of the alkoxyimino group and the photolysis of the beta-lactam ring. Cefuroxime axetil exists as a mixture of two diastereomers which are shown to react at different rates. This is true not only for the photoisomerization step but also for ground-state hydrolysis in alkaline conditions. Photoisomerization of the alkoxyimino group is also observed for the anti isomer of cefuroxime axetil and for some of its degradation products. The quantum yields for all these photoisomerizations are always lower than 1%, which explains the relative importance of the photolysis step. A stationary syn to anti ratio of 1 is measured for cefuroxime axetil and of 2.1 for cefuroxime. From this and previous studies, it appears that cefuroxime axetil is the most sensitive under irradiation at 254 nm when compared to other antibiotics bearing the alkoxyimino group. Azetreonam is the most stable followed by cefotaxime, cefuroxime, and cefuroxime axetil.
Cefuroxime↗
Photodegradation kinetics under UV light of aztreonam solutions.
A photodegradation study of aztreonam solutions exposed to UV irradiation showed that the major product of degradation was the anti-isomer together with some unidentified products. This result was similar to that obtained with cefotaxime and it is postulated that this would be generally true of compounds containing an alkoxyimino group.
Arginine↗
Determination of aminoglycosides in pharmaceutical formulations--I. Thin-layer chromatography.
A simple, fast and reliable procedure for the determination of seven major aminoglycosides in commercial formulations (injections, capsules, eye drops, solutions and ointments) is presented. The aminoglycosides are separated on silica gel plates then located with ninhydrin and analysed in situ using a chromatogram spectrophotometer. Linearity tests, repeatability (relative standard deviation congruent to 3.5%) detection limits (60-200 ng) were satisfactory for all the compounds. Recovery data in pharmaceutical formulations (expressed as the percentage of the label claim) from thin-layer chromatography (TLC) and microbiological assays did not give any significant difference (P = 0.05); this result shows that TLC is a reliable method for the determination of aminoglycosides as the drug substance and in pharmaceutical formulations.
Aminoglycosides↗
Determination of aminoglycosides in pharmaceutical formulations--II. High-performance liquid chromatography.
A post-column derivatization procedure using OPA and fluorescence detection has been used for the determination of seven aminoglycosides (dibekacin, framycetin, kanamycin, netilmicin, sisomicin, tobramycin and gentamicin) in commercial pharmaceutical formulations. The linearity, precision and detection limits were satisfactory. Recoveries from eye drops, ointments, injections and capsules were comparable (P = 0.05) to those obtained with TLC or microbiological assays. A ruggedness test showed that the method was not sensitive to minor variations in the mobile phase composition, post-column derivatization system or detection wavelength.
Aminoglycosides↗
Determination of cephalosporins and decomposition products by liquid chromatography with indirect electrochemical detection.
Explore the source record for details and available documents.
Cephalosporins↗
Photodegradation paths of cefotaxime.
The degradation kinetics of cefotaxime sodium salt in aqueous solution, under UV light at 254 nm, was investigated by HPLC and antibiotic activity. This degradation is the result of two competitive processes, an isomerization and a photolysis. This study is mostly about the isomerization step. The measured quantum yields for the cefotaxime to its anti-isomer and anti-isomer to cefotaxime isomerizations are, respectively, 0.10 and 0.12. A photostationary state characterized by an anti:syn ratio of 1.2 is obtained after 30 min of irradiation. The competitive photolysis, which actually consists of at least two processes (one on the delta 3-cephem ring and the second on the methoxyimino group), leads to an intense yellowing of the solution corresponding to the destruction of the molecule. The comparative evolution of the absorption spectra, under irradiation at 254 nm, of cefotaxime, thiazoximic acid, and 7-aminocephalosporanic acid shows that it is the delta 3-cephem ring photolysis which gives the yellow color. The major conclusion of this work is to call attention to the photoisomerization step which leads efficiently to the inactive anti-isomer, without giving any visible notice of degradation. Such a process is to be expected in all antibiotics containing an alkoxyimino linkage on the C-7 substitution.
Biological Assay↗