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A Rieutord

Publications and source records attributed to A Rieutord.

11 recordsLinked to original sources

Dual-mode gradient HPLC procedure for the simultaneous determination of chloroquine and proguanil.

In order to assay the antipaludic capsule of the Service de Santé des Armées (SSA), that contains two antimalarial drugs, i.e. chloroquine sulfate (CQS, cp1) and proguanil hydrochloride (PGH, cp5), a HPLC procedure was developed. A reversed-phase ion-pair high-performance liquid chromatography (HPLC) method with an ultraviolet detection at 254 nm was set up and validated. Elution system includes programming of both organic concentration and flow-rate known as 'dual-mode gradient'. This method allows the simultaneous determination of both active compounds and separation of four process related substances. The method is simple, rapid, selective and accurate, and the precision is good with an inter- and intra-assay of <2%. The sensitivity is particularly suitable for pharmaceutical quality control.

Antimalarials↗

Separation methods for alkylating antineoplastic compounds.

The separating method for alkylating neoplastic compounds were reviewed based on the classification of the Merck Index (12th Edition). Each section, whenever available or relevant, was subdivided according to the following approach: stability studies, extraction methods, gas chromatography, high-performance liquid chromatography and capillary electrophoresis. At the end of each chapter a separate table summarizing the main characteristics of the separating method were established. In particular LODs and/or LOQs were expressed as quantity to facilitate comparison between methods. This review highlights the problems to measure trace levels of these compounds into biological fluids with respect to their instability, adsorption to glass and plastic or derivatization requirements. Over the last decades, HPLC seems to be more popular than GC for separating the alkylating agents. The development of narrow- or microbore LC coupled to MS is certainly the way to further improve both separation and sensitivity obtained in the different papers surveyed for this review.

Antineoplastic Agents, Alkylating↗

Stability and sterility of meglumine gadoterate injection repackaged in plastic syringes.

The analytical and microbiological stability of meglumine gadoterate (Dotarem) repackaged in polypropylene syringe for 3 months at either +4 degrees C or room temperature was studied. For analytical study: six polypropylene syringes (20 ml) were filled with 15 ml of meglumine gadoterate. Three syringes were stored at 4+/-2 degrees C and three at 25+/-2 degrees C, all syringes were kept upright and protected from daylight. Samples were taken on days 0, 6, 14, 30, 45, 60, 75 and 90. Meglumine gadoterate and its degradation product (free Gd3+) concentrations were obtained using a specific HPLC assay. Osmolality and pH determination were made on days 0, 14, 45 and 90. For microbiological study: 28 plastic syringes (5 ml) were filled with 2.5 ml of meglumine gadoterate. Syringes were stored at 25+/-2 degrees C and protected from daylight. At each day of analysis (0, 15, 35, 45, 60, 75 and 90), four syringes were tested as described in European Pharmacopoeia. After 90 days the concentration of gadoterate remained unchanged and no free Gd3+ were detected. The injectable solution of this gadolinium contrast agent was sterile according to European Pharmacopoeia guidelines. The meglumine gadoterate repackaged in polypropylene syringe was stable for 3 months at all the temperatures studied.

Contrast Media↗

Quantitative determination of fat emulsion using 1,6-diphenyl-1,3,5-hexatriene as fluorescence probe: application to the compounding of all-in-one parenteral nutrition admixtures.

The potential contamination of binary bags by traces of fat emulsion stemmed from ternary bags prepared just before, led us to determine traces of lipids into the line set of the automated compounder MM23. Diphenylhexatriene (DPH) was chosen as fluorescence probe due to its strong fluorescence enhancement in a lipid environment. Optimization of experimental conditions (i.e. DPH amounts, pH of fat emulsion samples, ultrasounds use, light, temperature and contact duration) for fluorescence measurement and validation of analytical method were performed. This method was linear over 0.5-8.0 mg l(-1) (r=0.999) of fat emulsion. The intra-day and inter-day precisions were inferior to 2% for the 2.0 and 8.0 mg l(-1) standards. Under optimized conditions, the detection limit and quantitation limit were 0.10 and 0.29 mg l(-1) of lipids respectively. Compared to the colorimetric method using sodium dichromate, it is at least 100 times more sensitive. The proposed method permitted to rapidly measure fat emulsion traces in automated compounder line set for parenteral nutrition solutions and thus, to assess the risk of contamination of binary bags by lipids. At last, this method was shown to be conveniently applied to the analysis of fat emulsion in the final total parenteral nutrition bag.

Diphenylhexatriene↗

Quantitative high-performance liquid chromatographic determination of acrolein in plasma after derivatization with Luminarin 3.

A rapid, sensitive and specific high-performance liquid chromatographic method for the quantification of acrolein (1), one of the toxic metabolites of oxazaphosphorine alkylating agents (cyclophosphamide and ifosfamide) was developed. Condensation of acrolein with Luminarin 3 afforded a fluorescent derivative that could be specifically detected and quantified. Chromatographic conditions involved a C18 RP column Uptisphere and a gradient elution system to optimize resolution and time analysis. The method showed high sensitivity with a limit of detection of 100 pmol/ml and a limit of quantification of 300 pmol/ml. This technique is particularly suitable for pharmacokinetic studies on plasma of oxazaphosphorine-receiving patients.

Acrolein↗

Stability and compatibility of an aerosol mixture including N-acetylcysteine, netilmicin and betamethasone.

The physicochemical stability and the compatibility between N-acetylcysteine (1 g/5 ml), betamethasone (4 mg/1 ml) and netilmicin (100 mg/1 ml) were studied at room temperature (25+/-2 degrees C) over 1 h. During this study, drug concentrations were measured using three separate HPLC methods with UV detection at t=0, 5, 10, 20, 30, and 60 min. The pH of the mixture was determined. Degradation products of the drugs were assayed using HPLC. This study demonstrates the stability and compatibility of the mixture over 1 h at room temperature. The pinkish non-remnant coloration observed when pouring N-acetylcysteine into a recipient has no effect on the stability of the drug.

Acetylcysteine↗

Liquid chromatographic determination using lanthanides as time-resolved luminescence probes for drugs and xenobiotics: advantages and limitations.

Lanthanide sensitized luminescence is a very attractive alternative to UV detection and other luminescence techniques, i.e., fluorescence and phosphorescence, in separation science for the detection of drugs and xenobiotics because of the large Stokes shift, narrow emission bands and long lifetime. Some published applications of HPLC determination with lanthanide (Ln3+) sensitized luminescence detection are reviewed. Advantages and limitations of this technique are discussed. Normal-phase (NP) HPLC is not influenced by the quenching effect of water whereas reversed-phase (RP) HPLC is applicable to more compounds than NP-HPLC. However, pH adjustment and the quenching effect of water on Ln3+ luminescence are the main drawbacks of RP-HPLC. Elution properties and the need for pH adjustment are two arguments for selecting the mode of addition of Ln3+, i.e., pre- or post-column in the HPLC system. Sensitized Ln3+ luminescence detection is a much more specific method of detection than UV or fluorescence detection after HPLC separation but nevertheless, in some cases, does not always exhibit a significant increase in analytical performance when the donor itself is a strong fluorophore. The development of more powerful excitation sources could improve the limit of detection of the Ln3+ sensitized detection technique. This review suggests that it would be useful to obtain predicting factors about the drug to establish whether the latter is suitable to be measured using an HPLC-Ln3+ approach.

Chromatography, High Pressure Liquid↗

The influence of the sparteine/debrisoquine genetic polymorphism on the disposition of dexfenfluramine.

1. To determine whether dexfenfluramine is a substrate of cytochrome P450 2D6 (CYP2D6), its disposition has been studied in nine extensive (EM) and eight poor metabolizers (PM) of debrisoquine. 2. Following a 30 mg dose of dexfenfluramine hydrochloride, urine was collected in all subjects for 96 h post-dose and plasma samples were collected in 11 subjects (six EMs and five PMs). Dexfenfluramine and nordexfenfluramine were measured in urine by h.p.l.c. and in plasma by g.c. 3. Urinary recovery of dexfenfluramine was greater in PMs than EMs (4136 +/- 1509 micrograms vs 1986 +/- 792 micrograms; 95% CI of difference 926-3374; P < 0.05) whereas that of nordexfenfluramine was similar in both phenotypes (PM: 1753 +/- 411 micrograms vs 1626 +/- 444 micrograms). 4. Dexfenfluramine AUC was higher in PMs (677 +/- 348 micrograms l-1 h) than EMs 359 +/- 250 micrograms l-1 h). The apparent oral clearance of dexfenfluramine was greater in EMs than PMs (93.6 +/- 42.4 l h-1 vs 45.6 +/- 19.5 l h-1; 95% CI of difference 1.2-94.7; P < 0.05). The renal clearance was similar in both phenotypes (EMs: 5.88 +/- 2.83 l h-1; PMs 6.60 +/- 2.01 l h-1), indicating that the higher urinary recovery of dexfenfluramine in PMs reflects higher plasma concentrations, rather than phenotype differences in the renal handling, of dexfenfluramine. 5. The apparent nonrenal clearance of dexfenfluramine was substantially lower (P < 0.05; 95% CI of difference 3.0-94.1) in PMs (39.0 +/- 19.5 l h-1) than EMs (87.6 +/- 41.2 l h-1). 6. There was a significant inverse correlation (rs = 0.776 95% CI-0.31-0.94; n = 11; p = 0.005) between the debrisoquine metabolic ratio and the apparent nonrenal clearance of dexfenfluramine. 7. PMs had a higher incidence of adverse effects (nausea and vomiting) than EMs. 8. In conclusion, the metabolism of dexfenfluramine is impaired in PMs. Thus CYP2D6, the isoenzyme deficient in poor metabolizers of debrisoquine, must catalyse at least one pathway of dexfenfluramine biotransformation.

Adult↗

Gliclazide hydroxylation by rat liver microsomes.

1. The metabolism of gliclazide to hydroxygliclazide has been investigated in Sprague-Dawley rat liver microsomes. 2. The kinetics of hydroxygliclazide formation are consistent with Michaelis-Menten kinetics (mean (+/- SD, n = 3) apparent K(m) and Vmax = 256 +/- 27 microM and 1.85 +/- 0.10 nmol/ min/mg respectively). 3. Tolbutamide competitively inhibited hydroxygliclazide formation (Ki = 840 microM) and gliclazide competitively inhibited hydroxytolbutamide formation (Ki = 240 microM) with Ki similar to K(m). Therefore gliclazide and tolbutamide may be metabolized by the same enzyme in the rat. In nine livers the formation of hydroxygliclazide correlated with the formation of hydroxytolbutamide (rs = 0.82, p < 0.01). 4. Diclofenac (Ki = 64 microM), phenytoin (Ki = 38 microM), mephenytoin (Ki = 66 microM), glibenclamide (Ki = 14 microM) and glipizide (Ki = 189 microM) were fully competitive inhibitors of gliclazide hydroxylation. The rank order of Ki constants differed for gliclazide and tolbutamide suggesting that gliclazide and tolbutamide hydroxylases are not identical enzymes. 5. Quinine (Ki = 0.3 microM) and quinidine (Ki = 4.3 microM) were partially competitive inhibitors of hydroxygliclazide formation. Hydroxylation of gliclazide was related to the activity of CYP2D1 as assessed by dextrorphan production from dextromethorphan (rs = 0.83, p = 0.01). 6. In the rat gliclazide is metabolized to hydroxygliclazide by at least two cytochrome P450 isoforms, including tolbutamide hydroxylase and 2D1, which have similar affinities for gliclazide.

Animals↗

[Absence of chemical interaction between short catheters (ETFE) and three major antibiotics. Study model].

Recourse to sounding with vein catheters is more and more frequent in hospital environments. At the same time, a perceptible increase in incidents and accidents linked to this constantly growing practice is noted. The multiplication of new biomaterials used in the composition of catheters leads to taking into account the criteria of innocuousness and physiochemical inertia as discriminant elements in the choice of biomaterials. A study in vitro has been undertaken of the interaction between short catheters made of ethylenetetrafluoroethylen (ETFE) and antibiotic solutions widely used in hospital environments. The confrontation concerned solutions of vancomycine (Vancocin), ciprofloxacine (Ciflox) and the amoxicillin-clavulanic acid (Augmentin) association. A device has been fitted up and operative conditions have been set in order that the flushing out of the catheters by the solutions be in quality and quantity, as near as possible to actual conditions of use. The interaction marked chosen being a possible release of fluorides ions by the polymer, the determination of this anion has been made by liquid-gas chromatography paired with a flame ionization detection. We show the inertia of ETFE catheters with respect to the solutions examined. Taking into account the initially defined objectives, the conclusion of the work is important and constitutes a considerable factor of security for the catheters user whether he be buyer or practitioner. The model of study making up this approach could very be applied to other categories of materials and therapeutics.

Amoxicillin↗