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Jean-Luc Veuthey

Publications and source records attributed to Jean-Luc Veuthey.

At least 37 records · Page 2Linked to original sources
PubMed2005

Decreasing analysis time in capillary electrophoresis: validation and comparison of quantitative performances in several approaches.

Capillary electrophoresis (CE) can be used for the rapid determination of pharmaceuticals, particularly in routine quality control analysis. This paper focuses on several approaches aimed at decreasing the analysis time with commercially available instrumentation by (i) application of a high electric field through a reduced capillary, (ii) use of a dynamically coated capillary to increase the electroosmotic flow, (iii) short-end injection (SEI) technique, and (iv) application of multiple sample injections. Moreover, SEIs were combined with the three other approaches. A pharmaceutical formulation containing lidocaine as an active component was selected, and the methods were validated according to the ICH guidelines. The seven approaches investigated fulfilled different statistical requirements and demonstrated their linearity and trueness, with good recoveries and confidence limits always inferior to 1.5%. Furthermore, relative standard deviation (RSD) values for repeatability and intermediate precision were inferior to 1.1 and 1.8%, respectively. These results confirmed that each approach is of utmost interest to increase the analyte throughput in CE.

Electrophoresis, Capillary↗
PubMed2005

Rapid stereoselective separations of amphetamine derivatives with highly sulfated gamma-cyclodextrin.

The highly sulfated gamma-CD (HS-gamma-CD) is a chiral selector widely used in CE for the enantioseparation of pharmaceutical compounds. This paper investigated different approaches to reduce the stereoselective analysis time of amphetamine (AT) derivatives according to the chiral selector concentration in the BGE. With high HS-gamma-CD concentration, tested analytes were separated in 3.5 min as anionic complexes with short-end injection technique in reversed polarity mode. However, this procedure presented some limitations in terms of efficiency and resolution, excessive Joule heating and poor compatibility with MS detection. With low HS-gamma-CD concentration, compounds were separated as cations. Conventional approaches to reduce CE analysis time demonstrated critical resolution between some analytes. Therefore, the use of the partial-filling technique compatible with MS detection was carried out. Under optimized conditions, the analysis time for the chiral separation of seven AT like compounds was reduced to 6 min. Moreover, sensitivity of CE-MS was sufficient for the determination of ATs in plasma following a simple liquid-liquid extraction.

Amphetamines↗
PubMed2005

Capillary zone electrophoresis for the estimation of transdermal iontophoretic mobility.

The objective of the study was to investigate the relationship between transdermal iontophoretic flux--specifically, the electromigratory component--and electrophoretic mobility as determined by capillary zone electrophoresis (CZE). First, the steady-state iontophoretic transport rates of a series of dipeptides across porcine skin were determined in vitro. Co-iontophoresis of acetaminophen was used to quantify the respective contributions of electroosmosis (EO) and electromigration (EM). Second, the electrophoretic mobilities of the dipeptides and three other cationic drugs (lidocaine, propranolol, and quinine) were determined, under equivalent experimental conditions, using CZE. Analysis of the transport data using the results of the CZE experiments revealed a linear dependence (r2 > 0.9) between EM flux and electrophoretic mobility. The CZE measurements also provided insight into the charge state of "zwitterionic" dipeptides, H-Glu-epsilon-Lys-OH and H-Tyr-Gln-OH, revealing that these molecules had partial net negative charges under the formulation conditions, accounting for the absence of anodal iontophoretic delivery. The results suggest that CZE might (i) enable identification of ionization states of complex molecules, (ii) serve as a preliminary screen to identify electrically mobile compounds suitable for iontophoretic delivery, and (iii) prove useful for predicting the EM contribution to transdermal iontophoretic flux.

Acetaminophen↗
PubMed2005

Enantioseparation of baclofen with highly sulfated beta-cyclodextrin by capillary electrophoresis with laser-induced fluorescence detection.

The enantioseparation of baclofen (4-amino-3-p-chlorophenylbutyric acid) was achieved by CE-LIF with highly sulfated beta-CD (HS-beta-CD) as chiral selector. Naphthalene-2,3-dicarboxaldehyde was used for the derivatization of nonfluorescent baclofen. HS-beta-CD (2%) containing 50 mM borate buffer at pH 9.5 was chosen as the optimal running electrolyte and applied to the analysis of baclofen enantiomers in human plasma. The linearity of calibration curves (R2 > or = 0.998) for R-(-) and S-(+)-baclofen was in the 0.1-2.0 microM concentration range. After a simple ACN-protein precipitation, the LOD of baclofen in plasma sample was found as low as 50 nM.

Baclofen↗
PubMed2005

Novel RPLC stationary phases for lipophilicity measurement: solvatochromic analysis of retention mechanisms for neutral and basic compounds.

An RPLC was developed to rapidly determine lipophilicity of neutral and basic compounds using three base deactivated RPLC stationary phases particularly designed for the analysis of basic compounds, namely, Supelcosil ABZ(+)Plus, Discovery RP Amide C16, and Zorbax Extend C18. The work consisted of three sets of experiments. In the first log kw values of neutral compounds were extrapolated using hydroorganic mobile phases at different compositions. Good correlation between log kw and log Poct indicated that the method was appropriate for these supports, without adding a silanol masking agent. In the second set of experiments, isocratic log k values of neutral and basic compounds were measured with three different mobile phases. The best estimation of lipophilicity was obtained for neutral and basic compounds when the secondary interactions were strongly reduced (i. e., when basic compounds were under their neutral form). In the third set of experiments, isocratic retention factors of basic compounds (in their neutral form) were measured with a high-pH mobile phase, on a chemically stable support (Zorbax Extend C18). Under these chromatographic conditions, correlation between the isocratic retention factors and log Poct (log D10.5) for basic compounds was similar to that for neutral compounds.

Chromatography, Liquid↗
PubMed2005

Extraction and analysis of different Cannabis samples by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry.

A headspace solid-phase microextraction combined with GC-MS method was developed for the extraction and analysis of cannabinoids from Cannabis samples. Different commercially available fibres were evaluated; polydimethylsiloxane 100 microm was selected as the most efficient one. In order to enhance sensitivity and reduce analysis time, the sampling temperature was studied and it showed that extraction should be performed at a high temperature (150 degrees C). In relation with the high lipophilicity of cannabinoids, a relatively long desorption time (3 min) was necessary to ensure a total transfer from the fibre into the injection port of the gas chromatograph. The method was finally applied to the extraction of Swiss marijuana samples from different regions. Data treatment by principal component analysis and hierarchical cluster analysis allowed a discrimination of the different batches.

Cannabidiol↗
PubMed2005

Determination of pKa values by capillary zone electrophoresis with a dynamic coating procedure.

CZE allows to measure the acidic dissociation constant (pKa) of many drug substances. However, determining the EOF intensity may be time-consuming, especially at a low pH. In order to overcome this drawback, a dynamic coating procedure of the capillary was carried out to increase microEOF, and thus to reduce the analysis time. In addition, this coating procedure enhanced migration time stability. The effective mobilities of 15 compounds were measured at different pH, producing pK'a values dependent on BGE ionic strength. The latter values were corrected with the activity coefficient to obtain a "true" pKa value. The 15 investigated compounds were (i) five acids: namely, salicylic acid, benzoic acid, ketoprofen, phenobarbital, and phenol, (ii) four bases: lidocaine, propafenone, propranolol, and quinine, (iii), five ampholytes: sulfanilamide, sulfabenzamide, sulfadimethoxine, sulfadoxine, and sulfisoxazole, and (iv) one zwitterion: cetirizine. The range of determined pKa values was between 1.2 and 11.2, and close to the pKa values available from the literature.

Electrophoresis, Capillary↗
PubMed2004

Matrix effect in LC-ESI-MS and LC-APCI-MS with off-line and on-line extraction procedures.

Matrix effect on mass spectrometry response was investigated with commercially available electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) sources coupled with a single quadruple mass spectrometer. A post-column infusion system was used to observe the MS signal alterations of methadone, selected as the model compound, in plasma. For this purpose, two sample preparation procedures were tested: (1) conventional off-line sample preparations with liquid-liquid extraction (LLE), solid-phase extraction (SPE) and protein precipitation (PP) with perchloric acid (PA) and acetonitrile (ACN) and (2) on-line SPE with two different extraction columns packed with a large particle support (LPS) and with restricted access material (RAM), respectively. Whatever the sample preparation procedures, APCI source appeared to be less liable to matrix effect than ESI source. Among the different off-line sample preparations, LLE was the most efficient extraction procedure. With other techniques, MS signal was affected not only by endogenous material but also by procedure introduced compounds. Moreover, on-line SPE-LC-MS configuration exhibited matrix effects, which depend on the API source and the extraction support.

Chromatography, Liquid↗
PubMed2004

Ultrashort partial-filling technique in capillary electrophoresis for infinite resolution of tramadol enantiomers and its metabolites with highly sulfated cyclodextrins.

The possibility to enhance resolution to infinite value in chiral capillary electrophoresis is attained as soon as the apparent mobility of one enantiomer becomes opposite to the other. This could be achieved on the basis of the carrier ability of multiple charged chiral selectors such as highly sulfated cyclodextrin (HS-CD). With tramadol and its phase I metabolites selected as model compounds, the HS-gamma-CD was found to be the most appropriate chiral selector. The CD concentration was determined where one enantiomer still migrated as a cation while the other migrated in the opposite side. Besides the chiral selector concentration, secondary parameters such as buffer concentration appeared to be critical to reach infinite resolution. The latter was achieved with partial filling technique using ultrashort separation zones (a few mm). In order to better understand the interaction mechanism between the selected CD and the analytes, the classical affinity capillary electrophoresis method, although not fully satisfactory because of ionic strength variations within a series of mobility shift measurements, was applied to estimate complexation constants and complex mobilities. The results obtained point to the prevailing role of complex mobility differences in the enantioselectivity mechanism.

Buffers↗
PubMed2004

Analysis of basic compounds at high pH values by reversed-phase liquid chromatography.

Reversed phase high performance liquid chromatography (RPLC) is currently the method of choice for the analysis of basic compounds. However, with traditional silica materials, secondary interactions between the analyte and residual silanols produce peak tailing which can negatively affect resolution, sensitivity, and reproducibility. In order to reduce these secondary interactions, which comprise ion exchange, hydrogen bonding, and London forces interactions, chromatographic analyses can be carried out at low or high pH values where silanol groups and basic compounds are mostly uncharged. The chromatographic behaviour of a particular bidentate stationary phase, Zorbax Extend C18, was studied with a set of basic and neutral compounds. Thanks to a higher chemical stability than traditional silica based supports, analyses were carried out with a high pH mobile phase, which represents a good alternative to the acidic mobile phases generally used to reduce ion exchange interactions. The performance of this bidentate stationary phase was also compared with that of other supports and it was proved that it is advantageous to work with high pH mobile phases when analyzing basic compounds.

Chromatography, High Pressure Liquid↗
PubMed2004

Column-switching procedures for the fast analysis of drugs in biologic samples.

Liquid chromatography coupled with mass spectrometry in single and dual mode (LC-MS and LC-MS/MS) is the method of choice for the quantification of drugs and their metabolites in biologic fluids. Following the new challenges encountered in the process of drug development, liquid chromatography-mass spectrometry has been found to achieve high-throughput analysis. With this impressive tool, the sample preparation step before analysis is simplified, and the analytic process speeded up. Several generic approaches have recently been developed for the sample extraction coupled on line with a LC-MS system. In this paper, different extraction supports allowing the direct injection of biologic fluids were investigated, namely, restricted-access media, large-size particle, and monolithic phases. In the column-switching configuration, these supports, coupled with microbore analytic columns, were found suitable for the fast analysis (total analysis time of less than 10 minutes) of different drugs and their metabolites in biologic matrices at the nanogram per milliliter level.

Chromatography, Liquid↗
PubMed2003

Time course of clinical response to venlafaxine: relevance of plasma level and chirality.

OBJECTIVE: Early clinical response to antidepressant treatment is an important therapeutic goal, considering the psychological, social and economic consequences of depression. The aim of the present study was to investigate the relationship between the time course of response and the concentration of venlafaxine (V), its active metabolite O-desmethylvenlafaxine (ODV) and enantiomeric ratios V(+)/V(-) and ODV(+)/ODV(-). METHODS: Depressed inpatients ( n=35) received V orally at a fixed 300 mg daily dose. Accepted comedication included clorazepate (maximum 60 mg/day), zopiclone (maximum 15 mg/day) and low-dose trazodone (maximum 200 mg/day). Severity of depression was assessed on days 0, 4, 7, 11, 14, 21 and 28 (Montgomery and Asberg Depression Rating Scale). Blood samples were taken on day 14 and day 28 and submitted to stereoselective determination. All measurements reflected trough steady-state values. First, pattern analysis was used to provide a categorical perspective of clinical response (50% improvement from baseline depression score). Patients displaying non-response, transient response, early persistent response and delayed persistent response were compared with respect to racemic concentrations and enantiomeric ratios. Second, in a dimensional perspective, mixed-effects modelling was used to analyse severity of depression versus time curves with respect to the possible influence of concentrations and enantiomeric ratios. RESULTS: Comparison of patients with and without persistent response did not reveal any significant difference for V, ODV, V+ODV plasma levels or enantiomeric ratios. Persistent response was significantly associated with less frequent pre-study antidepressant medication and less frequent comedication with zopiclone (day 14) and clorazepate (day 28) during the study. Focus on patients with persistent response ( n=19, 54.3%) indicated that early response, first observed before day 14, was associated with significantly higher V+ODV concentration than delayed response (median 725 ng/ml versus 554 ng/ml, P=0.023). No difference was found for pre-study medication or comedication during the study. Shorter time to onset of response was significantly associated with lower V(+)/V(-) enantiomeric ratio (r(s)=0.48, P<0.05). Mixed-effects modelling of depression severity versus time curves in patients with persistent response confirmed that either higher V+ODV plasma level or lower V(+)/V(-) ratio were significantly associated with more rapid decrease of depression score (likelihood ratio tests, P=0.012 and P=0.046, respectively). CONCLUSION: Considering its modest sample size, naturalistic design and limited observation period, the present study provided preliminary indication that earlier clinical response may occur with higher V+ODV plasma level, extending previous dose-response studies. The hypothesis was also raised that exposure to a more potent noradrenergic therapeutic moiety, as reflected by a lower V(+)/V(-) ratio, may be relevant to early improvement of depression.

Adult↗
PubMed2003

Simultaneous analysis of metabisulfite and sulfate by CE with indirect UV detection. Application to and validation for a pharmaceutical formulation.

Metabisulfite is used as an antioxidant agent in a number of pharmaceutical formulations. In order to quantify simultaneously both metabisulfite and its oxidation product (sulfate), a capillary zone electrophoretic (CZE) method with indirect UV detection was developed. Best results were achieved with a background electrolyte (BGE) constituted of 15 mM pyromellitic acid, 15 mM tris-(hydroxymethyl)-aminomethane and 0.2 mM tetradecyltrimethylammonium bromide at pH 8.3 and an applied electrical field of 123 V/cm in a 32.5 cm fused silica capillary. Indirect UV detection was performed at a wavelength of 225 nm. In order to validate this method, an internal standard (IS), namely ammonium formate, was used. Moreover, due to the high chloride concentration in the pharmaceutical formulation, conductivity was adjusted by adding sodium chloride into standard solutions to prevent matrix effect. Linearity and accuracy were successfully tested in a concentration range of 33.3-250 microg/ml for sodium metabisulfite and of 50-375 microg/ml for sodium sulfate. Method precision was determined on six samples each day. Thereby, relative standard deviations (R.S.D.) of 6% and 12-13% were obtained for intra-day and inter-day precision, respectively. Considering the instability of metabisulfite and its use as an antioxidant agent and not as an active principle, the method was accepted and used for routine analyses.

Chemistry, Pharmaceutical↗
PubMed2003

Influence of electrolyte nature on the separation selectivity of amphetamines in nonaqueous capillary electrophoresis: protonation degree versus ion pairing effects.

The simultaneous analysis of Ecstasy and its derivatives in an acetonitrile-methanol (80:20 v/v) mixture was previously shown to be strongly dependent on the nature of the electrolyte (acetate versus formate). To elucidate the phenomena involved, systematic experiments were conducted in this solvent medium. Conductivity measurements allowed to evaluate the ion-pairing rate in the background electrolyte (BGE) and thereby distinguish between electrolyte concentration and ionic strength. The influence of electrolyte concentration on analyte effective mobilities micro(eff)) was studied by capillary electrophoresis (CE). As micro(eff) extrapolated to infinite dilution proved to be independent of the nature of the electrolyte, selectivity changes could not be attributed to a modification in the protonation degree of amphetamines. Experimental mobility data were then confronted to existing theoretical mobility models to discriminate between ion pairing or simple ionic strength effect. Ion-pair formation in a BGE containing acetate was highlighted with an ion-pairing model and ion-pair formation constants between each amphetamine and acetate ion were calculated.

Amphetamines↗
PubMed2003

Infinite enantiomeric resolution of basic compounds using highly sulfated cyclodextrin as chiral selector in capillary electrophoresis.

Four chiral basic analytes, namely methadone, fluoxetine, venlafaxine, and tramadol, were selected as model compounds for investigating their stereoselective separation with highly sulfated gamma-cyclodextrin (HS gamma-CD) by capillary electrophoresis (CE)-UV and CE-mass spectrometry (MS). At high concentration of chiral selector, the preferentially bonded enantiomer migrated faster in the anodic mode to the detector and high resolutions were obtained for all analytes. In the cathodic mode, at lower highly sulphated cyclodextrin (HS-CD) concentration, basic compounds could be detected, with the weakly bonded enantiomer migrating first (enantiomeric migration order inversion). It was also then possible, at intermediate HS-CD concentration, that only one enantiomer migrated to the detector as cation while the other enantiomer complexed with the CD was negatively charged and presented an opposite mobility. The latter never reached the detector achieving a perfect enantiomeric selectivity. Infinite chiral resolutions were thus achieved by CE-UV as well as by CE-electrospray ionisation (ESI)-MS where concentrations of HS-CD were adapted according to the negative contribution of the nebulization gas pressure of the interface.

Cyclodextrins↗
PubMed2003

Validation of capillary electrophoresis--mass spectrometry methods for the analysis of a pharmaceutical formulation.

The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) with an electrospray ionization (ESI) technique is generally performed for qualitative applications, and only few quantitative results have been reported. This paper investigates the validation of a CE-ESI-MS method for the analysis of a pharmaceutical formulation containing lidocaine. Some important ESI criteria are discussed including sheath-liquid composition, nebulizing gas pressure and position of the CE capillary outlet. After optimization of these parameters, an intermediate precision of about 5% was achieved. The latter, as well as efficiency and resolution, were compared to those achieved with UV detection. Besides, a multiple injection procedure was developed to reduce analysis time per sample and was successfully applied to both UV and MS detectors. The validation results achieved by multiple injections were identical to those obtained with classical injection, but afforded a gain of time by a factor of 2.5.

Anesthetics↗
PubMed2003

Analysis of selected withanolides in plant extract by capillary electrochromatography and microemulsion electrokinetic chromatography.

Microemulsion electrokinetic chromatography (MEEKC) coupled with a diode-array detector was developed for the simultaneous analysis of natural steroidal compounds, withanolides including withaferin A, withacnistin and iochromolide. Optimal resolution was obtained with a microemulsion consisting of 70 mM octane, 800 mM 1-butanol, 100 mM sodium dodecyl sulfate (SDS), and 10 mM phosphate-borate buffer (pH 7) using a fused-silica capillary at 25 kV and 40 degrees C. Since this technique is not compatible with mass spectrometry detection, a capillary electrochromatographic method was developed to separate the investigated withanolides. The effects of mobile phase composition and pH were systematically investigated. Complete separation was obtained with a capillary electrochromatography (CEC) Hypersil C18 bonded silica column (packed length, 25 cmx100 microm ID and 375 microm OD), packed with 3 microm particles. The mobile phase consisted of formic acid-ammonia, pH 8 / acetonitrile (40/60 v/v); the voltage was set at 25 kV and the temperature at 20 degrees C. Under these conditions, resolution of these closely related compounds, including the critical pair withacnistin and iochromolide, was achieved in less than 5 min. The separations by MEEKC and CEC were compared with that obtained by reversed-phase liquid chromatography and showed similar retention order, indicating the analogy of the retention mechanism of these techniques. To further improve specificity and sensitivity, the developed CEC method was interfaced with electrospray ionization mass spectrometry using a Teflon connection between the CEC column and a void fused-silica capillary. Finally, the described methods were applied to the qualitative analysis of withanolides in Iochroma gesnerioides plant extract.

Chromatography, Micellar Electrokinetic Capillary↗