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Biomedical subjects

J Crommen

Publications and source records attributed to J Crommen.

At least 37 records · Page 2Linked to original sources
PubMed2002

Strategy for the development of automated methods involving dialysis and trace enrichment as on-line sample preparation for the determination of basic drugs in plasma by liquid chromatography.

Among the sample preparation techniques, dialysis followed by clean-up and enrichment of the dialysate on a pre-column has proved to be a useful approach for the LC determination of drugs in plasma. By use of sample processors, like the ASTED system, such bioanalytical methods can be fully automated, the dialysis and trace enrichment steps being directly coupled to LC. In order to facilitate the development of such automated methods, a strategy based on a decision tree has been elaborated. After the selection of appropriate conditions for the LC analysis, the decision tree provides information about suggested starting conditions and guidelines for the optimisation of the most important parameters likely to influence analyte recovery and method selectivity. The plasma samples are dialysed on a cellulose acetate membrane in the static-pulsed mode and the dialysate is enriched on a trace enrichment pre-column packed with octadecyl silica or with a strong cation-exchange material. This decision tree is until now restricted to the analysis of basic drugs in plasma. In order to demonstrate the applicability of this method development strategy, an automated procedure based on the coupling of dialysis with trace enrichment has been developed for the LC determination of antifungal agents (clotrimazole, econazole and miconazole) in plasma.

Antifungal Agents↗
PubMed2002

Automated determination of pirlindole enantiomers in plasma by on-line coupling of a pre-column packed with restricted access material to a chiral liquid chromatographic column.

A fully automated liquid chromatographic method has been developed for the determination of the enantiomers of pirlindole, an antidepressant drug, in human plasma. The method is based on the use of a pre-column packed with restricted access material (RAM) (LiChrospher ADS RP-4) for sample clean-up coupled to a column containing a cellulose tris-(3,5-dimethylphenylcarbamate) based chiral stationary phase (Chiralcel OD-R) for the separation and quantitative analysis of pirlindole enantiomers. A 50-microl plasma volume was injected directly onto the pre-column using a mixture of phosphate buffer (pH 5.0) and methanol (97:3; v/v) as washing liquid. By rotation of a switching valve, the analytes were then eluted in the back-flush mode with the LC mobile phase. A complete separation of pirlindole enantiomers was obtained in 22 min on the Chiralcel OD-R column, using a mobile phase made of a mixture of phosphate buffer (pH 5.0) containing 50 mM sodium perchlorate and acetonitrile (65:35; v/v). The flow-rate was 0.6 ml/min and the analytes were detected fluorometrically using 295 and 340 nm as excitation and emission wavelengths, respectively. The method was then validated and was found to be linear in the 2.5-200 ng/ml range. The limit of detection was lower than 1 ng/ml. Repeatability and intermediate precision at a concentration of 50 ng/ml were about 1.5 and 3.5%, respectively.

Antidepressive Agents↗
PubMed2001

On-line coupling of partial filling-capillary zone electrophoresis with mass spectrometry for the separation of clenbuterol enantiomers.

The on-line coupling of capillary zone electrophoresis with mass spectrometry (CZE-MS) for the separation of enantiomers is hampered by the presence of nonvolatile chiral selectors such as cyclodextrins in the separation buffer. This problem can be overcome by use of the partial filling technique where only a part of the capillary is filled with the separation buffer containing chiral selectors. Since the electroosmotic flow is almost completely suppressed at acidic pH, that dimethyl-beta-cyclodextrin is neutral, no free cyclodextrin would reach the MS detector when using a partially filled capillary. By this method, clenbuterol enantiomers were successfully resolved and separated from salbutamol (internal standard) in aqueous solution and in plasma samples. A solid-phase extraction (SPE) was used for the preparation of plasma samples before analysis.

Clenbuterol↗
PubMed2001

Development and validation of an automated method for the liquid chromatographic determination of sotalol in plasma using dialysis and trace enrichment on a cation-exchange pre-column as on-line sample preparation.

A fully automated method for the determination of sotalol in human plasma was developed, involving dialysis through a cellulose acetate membrane, clean-up and enrichment of the dialysate on a strong cation-exchange pre-column and subsequent liquid chromatographic (LC) analysis with UV detection. All sample handling operations were carried out by means of an ASTED system. Before starting dialysis, the trace enrichment column (TEC) was conditioned. The plasma sample, to which the internal standard (atenolol) was automatically added, was then loaded in the donor channel and was kept static while the dialysis liquid, consisting of 0.017 M acetic acid, was passed through the acceptor channel in successive pulses. After each pulse, the dialysate was dispensed onto the TEC. When dialysis was discontinued, the analytes were eluted from the TEC by the LC mobile phase by rotation of a switching valve and transferred to the analytical column packed with octyl silica. The LC mobile phase was a mixture of methanol and pH 7.0 phosphate buffer containing 1-octanesulfonate at a concentration of 7.5 x 10(-4) M (19:81; v/v). The UV detection was performed at 230 nm. The influence of several parameters of the dialysis and trace enrichment processes on analyte recovery and method selectivity was investigated. The method was then validated. The mean absolute recovery for sotalol was about 60%. The limit of quantitation was 25 ng/ml and R.S.D. for repeatability and intermediate precision obtained at a concentration level of 50 ng/ml were 4.3 and 5.8%, respectively.

Automation↗
PubMed2000

Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography using mass spectrometric detection.

The chiral synthesis of beta-blockers such as (S)-timolol requires a sensitive analytical method for the enantioseparation of its intermediate, 3-tert.-butylamino-1,2-propanediol, in the ng/ml range. The method developed is based on on-line normal-phase LC-MS-MS using a chiral stationary phase and an atmospheric pressure chemical ionization (APCI) interface. The MS detection of 3-tert.-butylamino-1,2-propanediol was first optimized with a pneumatically-assisted electrospray interface (ionspray). The APCI interface was then selected for LC-MS-MS because of the incompatibility of electrospray with n-hexane. The method was validated for both enantiomers in the 25-500 ng/ml concentration range.

Atmospheric Pressure↗
PubMed2000

Quantitative analysis of N-acetylcysteine and its pharmacopeial impurities in a pharmaceutical formulation by liquid chromatography-UV detection-mass spectrometry.

A new method for the simultaneous determination of N-acetylcysteine and its pharmacopeial impurities, cysteine, cystine, N,N'-diacetylcystine and N,S-diacetylcysteine in an effervescent tablet has been developed. The method is based on on-line LC-UV-MS using a pneumatically-assisted electrospray interface (ionspray). The stability of the thiol moieties of the analytes was ensured by the acidic pH of the LC mobile phase. Quantitation of N-acetylcysteine was performed with UV detection to avoid ion-source overloading effect due to its higher concentration, whereas the impurities could be easily separated and quantified in MS. The method was validated in terms of stability, linearity, precision and accuracy.

Acetylcysteine↗
PubMed2000

Enantioseparation of anionic analytes by non-aqueous capillary electrophoresis using quinine and quinidine derivatives as chiral counter-ions.

A non-aqueous capillary electrophoretic method developed for the enantioseparation of N-protected amino acids has been applied to the investigation of five new quinine and quinidine derivatives as chiral selectors: 1-adamantyl carbamoylated quinine, 3,4-dichlorophenyl carbamoylated quinidine, allyl carbamoylated dihydroquinine, allyl carbamoylated dihydroquinidine and 1-methyl quininium iodide. The composition of the background electrolyte was 12.5 mM ammonia, 100 mM octanoic acid in an ethanol-methanol (60:40 v/v) mixture containing a 10 mM concentration of the chiral selector. Under these conditions, the enantioseparation of a series of various benzoyl, 3,5-dinitrobenzoyl and 3,5-dinitrobenzyloxycarbonyl amino acid derivatives was studied with respect to selectand-selector relationship and enantioselectivity.

Anions↗
PubMed2000

Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography coupled to evaporative light scattering detection.

A method for the separation and quantitation of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography and evaporative light scattering detection has been developed. Separation of the enantiomers was performed in normal-phase liquid chromatography on a Chiralpak AS chiral stationary phase. The influence of the gas nature, gas pressure and temperature of the drift tube of the evaporative light scattering detector on the detection sensitivity was investigated. The method was validated in terms of linearity, limit of quantitation, accuracy and precision. The enantiomeric excess of (S)-3-tert.-butylamino-1,2-propanediol, used for the industrial synthesis of (S)-timolol, was measured from 0 to 94%.

Chromatography, High Pressure Liquid↗
PubMed2000

Non-aqueous capillary electrophoretic enantioseparation of N-derivatized amino acids using cinchona alkaloids and derivatives as chiral counter-ions.

A non-aqueous capillary electrophoretic method developed with quinine and tert.-butyl carbamoylated quinine as chiral selectors for the enantioseparation of N-protected amino acids was applied to the investigation of other quinine derivatives as chiral additives. The optimum composition of the background electrolyte was found to be 12.5 mM ammonia, 100 mM octanoic acid and 10 mM chiral selector in an ethanol-methanol (60:40, v/v) mixture. Under these conditions, a series of chiral acids, as various benzoyl, 3,5-dinitrobenzoyl and 3,5-dinitrobenzyloxycarbonyl amino acid derivatives were investigated with regards to selectand-selector relationships and enantioselectivity employing quinine, quinidine, cinchonine, cinchonidine, tert.-butyl carbamoylated quinine, tert.-butyl carbamoylated quinidine, dinitrophenyl carbamoylated quinine and cyclohexyl carbamoylated quinine as chiral selector.

Amino Acids↗
PubMed2000

Enantiomeric separations of drugs using mixtures of charged and neutral cyclodextrins.

An overview on the use of mixtures of neutral and charged cyclodextrins as chiral additives for the enantioseparation of drugs by capillary electrophoresis is presented. These so called dual cyclodextrin systems can often provide unique selectivities. A brief theoretical background illustrating the influence of the chiral discrimination ability and the effective mobility of the two cyclodextrins on the overall selectivity of the enantiomeric separation is given. Typical examples of applications in the pharmaceutical field, based on the simultaneous use of a charged (cationic or anionic) and neutral cyclodextrins, are described.

Cyclodextrins↗
PubMed2000

Automated liquid chromatographic determination of atenolol in plasma using dialysis and trace enrichment on a cation-exchange precolumn for sample handling.

A fully automated method involving dialysis combined with trace enrichment was developed for the liquid chromatographic (LC) determination of atenolol, a hydrophilic beta-blocking agent, in human plasma. The plasma samples were dialysed on a cellulose acetate membrane and the dialysate was reconcentrated on a short trace enrichment column (TEC) packed with a strong cation-exchange material. All sample handling operations can be executed automatically by a sample processor (ASTED system). After TEC conditioning, the plasma sample, to which the internal standard (sotalol, another hydrophilic beta-blocker) was automatically added, was introduced in the donor channel and dialysed in the static/pulsed mode. The dialysis liquid consisted of 4.3 mM phosphoric acid. When the dialysis process was discontinued, the analytes were eluted from the TEC in the back-flush mode by the LC mobile phase and transferred to the analytical column, packed with octyl silica. The LC mobile phase consisted of phosphate buffer, pH 7.0-methanol (81:19; v/v) with 1-octanesulfonate. Atenolol and the internal standard were monitored photometrically at 225 nm. The different parameters influencing the dialysis and trace enrichment processes were optimised with respect to analyte recovery. The influence of two different kinds of cation-exchange material on analyte recovery and peak efficiency was also studied. The method was then validated in the concentration range 25-1000 ng/ml. The mean recovery for atenolol was 65% and the limit of quantitation was 25 ng/ml.

Adrenergic beta-Antagonists↗
PubMed2000

Enantiomeric separation of clenbuterol by transient isotachophoresis-capillary zone electrophoresis-UV detection new optimization technique for transient isotachophoresis.

A method for the in-line preconcentration and enantioseparation of clenbuterol by transient isotachophoresis-capillary zone electrophoresis-UV absorbance detection (transient ITP-CZE-UV) has been developed. It implies the use of dimethyl-beta-cyclodextrin as chiral selector and the application of a hydrodynamic counterflow during the ITP step. ITP is used to focus the sample constituents prior to CE whereas a counterpressure counterbalances the electrophoretic migration of the compounds. The sample is then focused and kept stationary in the proximity of the capillary inlet before CZE separation, leading to an extended-volume ITP-CZE system. A new strategy for the fast optimization of the counterpressure has been developed which implies the measurement of the hydrodynamic and electrophoretic velocities of the analyte during ITP. The in-line preconcentration and enantioseparation of clenbuterol selected as model compound was optimized using this method. Salbutamol was chosen as internal reference in order to check the reproducibility of the method. A 173-nl volume of aqueous ample solution was injected which implies an improvement of the injection volume of about 16 and a resolution of 4.8 was obtained for the clenbuterol enantiomers. A concentration detection limit of 10(-6) mol/l was readily achieved for clenbuterol and salbutamol using only 3 min ITP preconcentration in in-line counterflow transient ITP-CZE-UV. Thanks to its fast optimization, the method is applicable to any enantioseparation by means of only five very short preliminary measurements.

Clenbuterol↗
PubMed2000

Determination of albendazole and its main metabolites in ovine plasma by liquid chromatography with dialysis as an integrated sample preparation technique.

Albendazole is a benzimidazole derivative with a broad-spectrum activity against human and animal helminth parasites. In order to determine the main pharmacokinetic parameters in sheep after oral and intravenous administration of a new formulation of albendazole (an aqueous solution), a fully automated method was developed for the determination of this drug and its main metabolites, albendazole sulfoxide (active metabolite) and sulfone in ovine plasma. This method involves dialysis as purification step, followed by enrichment of the dialysate on a precolumn and liquid chromatography (LC). All sample handling operations were executed automatically by means of an ASTED XL system. After conditioning of the trace enrichment column (TEC) packed with octadecyl silica with pH 6.0 phosphate buffer containing sodium azide, the plasma sample, in which a protein releasing reagent (1 M HCl) containing Triton X-100 was automatically added, was loaded in the donor channel and dialysed on a cellulose acetate membrane in the static-pulsed mode. The dialysis liquid consisted of pH 2.5 phosphate buffer. By rotation of a switching valve, the analytes were eluted from the TEC in the back-flush mode by the LC mobile phase and transferred to the analytical column, packed with octyl silica. The chromatographic separation was performed at 35 degrees C and the analytes were monitored photometrically at 295 nm. Due to the differences in hydrophobic character between albendazole and its metabolites, a gradient elution was applied. The mobile phase consisted of a mixture of acetonitrile and pH 6.0 phosphate buffer. The proportion of organic modifier was increased from 10.0 to 50.1% in 12.30 min, then from 50.1 to 66.9% in 1.70 min. First, the gradient conditions and the temperature were optimised for the LC separation using the DryLab software. Then, the influence of some parameters of the dialysis process on analyte recovery was investigated. Finally, the method developed was validated. The mean recoveries for albendazole and its metabolites were about 70 and 65%, respectively. The limits of quantification for albendazole and its metabolites were 10 and 7.5 ng/ml, respectively.

Albendazole↗
PubMed2000

Comparative evaluation of four detectors in the high-performance liquid chromatographic analysis of chiral nonaromatic alcohols.

A comparative evaluation of ultraviolet, polarimetric, refractive index, and evaporative light-scattering detection coupled with high-performance liquid chromatography has been developed for the separation and quantitation of the enantiomers of chiral nonaromatic alcohols, some of which are intermediates in the synthesis of chiral drugs. (R,S)-3-tert-butylamino-1,2-propanediol; (R,S)-glycidol; and (R,S)-1-(4-morpholino)-2-octanol are selected as model compounds in order to compare the detection sensitivity and the linearity of the response with the four detectors. Separation of the enantiomers is performed using chiral stationary phases in normal-phase liquid chromatography. A one-day validation is achieved for (S)-3-tert-butylamino-1,2-propanediol with each detector, and limits of quantitation are determined for the three compounds. Advantages and limitations of the four detectors are discussed.

Alcohols↗