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Dive into the research topics where Jan Van Bocxlaer is active.

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Featured researches published by Jan Van Bocxlaer.


Journal of Chromatography B | 2002

Simultaneous, quantitative determination of opiates, amphetamines, cocaine and benzoylecgonine in oral fluid by liquid chromatography quadrupole-time-of-flight mass spectrometry.

Kjell A. Mortier; Kristof E. Maudens; Willy Lambert; Karine M. Clauwaert; Jan Van Bocxlaer; Dieter Deforce; Carlos Van Peteghem; André P. De Leenheer

A method using liquid chromatography coupled to tandem mass spectrometry is described for the determination of drugs of abuse in oral fluid. The method is able to simultaneously quantify amphetamines (amphetamine, methamphetamine, MDA, MDMA and MDEA), opiates (morphine and codeine), cocaine and benzoylecgonine. Only 200 micro of oral fluid is spent for analysis. The sample preparation is easy and consists of mixed mode phase solid-phase extraction. Reversed-phase chromatography is carried out on a narrow bore phenyl type column at a flow-rate of 0.2 ml/min. A gradient is applied ranging from 6 to 67.6% methanol with ammonium formate (10 mM, pH 5.0) added to the mobile phase. The column effluent was directed into a quadrupole-time-of-flight instrument by electrospray ionization, without the use of a splitter. A validation study was carried out. Recovery ranged from 52.3 to 98.8%, within-day and between-day precision expressed by relative standard deviation were less than 11.9 and 16.8%, respectively, and inaccuracy did not exceed 11.6%. The limit of quantification was 2 ng/ml (0.66 x 10(-5)-1.48 x 10(-5) M) for all compounds. Internal standards were used to generate quadratic calibration curves (r(2)>0.999). The method was applied to real samples obtained from suspected drug users. An interference was observed from the device used to sample the oral fluid, consequently this was excluded from the method which was validated on oral fluid obtained by spitting in a test-tube.


Journal of Chromatography B | 2009

Joint GC-MS and LC-MS platforms for comprehensive plant metabolomics: repeatability and sample pre-treatment.

Ruben t’Kindt; Kris Morreel; Dieter Deforce; Wout Boerjan; Jan Van Bocxlaer

Metabolomics nowadays mostly comprises the application of both LC-MS and GC-MS based approaches. Here we investigate different extraction set-ups for these two established analytical platforms in the field of plant metabolomics. Six extraction approaches for Arabidopsis thaliana leaves, varying in extraction solvent composition, extraction temperature and order of solvent addition within the extraction sequence, were analyzed on the two platforms. Our aim was to establish the most suitable analysis protocol, practicable for both LC-MS and GC-MS analysis, in order to obtain as extensive as possible metabolome coverage. One single sample preparation procedure would save time and valuable sample while still offering the complementary datasets generated by GC-MS and LC-MS. All extraction approaches were evaluated based on the following criteria: number of detected m/z-retention time pairs, heat maps of the detected peaks, and residual enzymatic activity of invertase and phosphatase in the plant leaf extracts. Unsupervised principal component analysis (PCA) was used to evaluate grouping trends between the different extraction approaches. Quality controls, a blend of aliquots of the different extracts, were used to establish a paired evaluation of the repeatability performance of the GC-MS and LC-MS analysis. We conclude that the use of chloroform in the extraction solvent is counterproductive in an untargeted LC-MS metabolomics approach as is heating. Below room temperature (instead of heated) extraction does not significantly degrade GC-MS performance but one should be more cautious with respect to residual enzymatic activity in the plant extract.


Anesthesiology | 2007

Influence of administration rate on propofol plasma - Effect site equilibration

Michel Struys; Marc Coppens; Nikolaas De Neve; Eric Mortier; Anthony G. Doufas; Jan Van Bocxlaer; Steven L. Shafer

Background:The authors hypothesized a difference in plasma–effect site equilibration, depicted by a first-order constant ke0, depending on the injection rate of propofol. Methods:Sixty-one patients received 2.5 mg/kg propofol given as a bolus or as a 1-, 2-, or 3-min infusion. The Bispectral Index was used to monitor drug effect. Propofol predicted plasma concentration was calculated using a three-compartment model and the effect site concentration over time as the convolution between the predicted plasma concentration and the disposition function of the effect site concentration. The authors evaluated the influence of the infusion rate on the ke0 by comparing the model with one ke0 for all groups with models estimating different ke0 values for each group. The authors also assessed the accuracy of two pharmacokinetic models after bolus injection. Results:The best model based was a fixed (Bispectral Index ≥ 90) plus sigmoidal model (Bispectral Index < 90) with two values of ke0, one for the bolus (t½ ke0 = 1.2 min) and one for the infusions (t½ ke0 = 2.2 min). However, the tested pharmacokinetic models poorly predicted the arterial concentrations in the first minutes after bolus injection. Simulations showed the requirement for two ke0 values for bolus and infusion was mostly a compensation for the inaccurate prediction of arterial concentrations after a bolus. Conclusion:Propofol plasma–effect site equilibration occurs more rapidly after a bolus than after rapid infusion, based on the electroencephalogram as a drug effect measure, mostly because of misspecification of the pharmacokinetic model in the first minutes after bolus.


Journal of Environmental Monitoring | 2009

JEM Spotlight: Fungi, mycotoxins and microbial volatile organic compounds in mouldy interiors from water-damaged buildings

Viviana Polizzi; Barbara Delmulle; An Adams; Antonio Moretti; Antonia Susca; Anna Maria Picco; Yves Rosseel; Ruben't Kindt; Jan Van Bocxlaer; Norbert De Kimpe; Carlos Van Peteghem; Sarah De Saeger

Concerns have been raised about exposure to mycotoxin producing fungi and the microbial volatile organic compounds (MVOCs) they produce in indoor environments. Therefore, the presence of fungi and mycotoxins was investigated in 99 samples (air, dust, wallpaper, mycelium or silicone) collected in the mouldy interiors of seven water-damaged buildings. In addition, volatile organic compounds (VOCs) were sampled. The mycotoxins were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (20 target mycotoxins) and quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Morphological and molecular identifications of fungi were performed. Of the 99 samples analysed, the presence of one or more mycotoxins was shown in 62 samples by means of LC-MS/MS analysis. The mycotoxins found were mainly roquefortine C, chaetoglobosin A and sterigmatocystin but also roridin E, ochratoxin A, aflatoxin B(1) and aflatoxin B(2) were detected. Q-TOF-MS analysis elucidated the possible occurrence of another 42 different fungal metabolites. In general, the fungi identified matched well with the mycotoxins detected. The most common fungal species found were Penicillium chrysogenum, Aspergillus versicolor (group), Chaetomium spp. and Cladosporium spp. In addition, one hundred and seventeen (M)VOCs were identified, especially linear alkanes (C(9)-C(17)), aldehydes, aromatic compounds and monoterpenes.


Anesthesiology | 2011

An Evaluation of Using Population Pharmacokinetic Models to Estimate Pharmacodynamic Parameters for Propofol and Bispectral Index in Children

Marc Coppens; Douglas J. Eleveld; Johannes H. Proost; Luc Marks; Jan Van Bocxlaer; Hugo Vereecke; Anthony Absalom; Michel Struys

Background:To study propofol pharmacodynamics in a clinical setting a pharmacokinetic model must be used to predict drug plasma concentrations. Some investigators use a population pharmacokinetic model from existing literature and minimize the pharmacodynamic objective function. The purpose of the study was to determine whether this method selects the best-performing pharmacokinetic model in a set and provides accurate estimates of pharmacodynamic parameters in models for bispectral index in children after propofol administration. Methods:Twenty-eight children classified as American Society of Anesthesiologists physical status 1 who were given general anesthesia for dental treatment were studied. Anesthesia was given using target-controlled infusion of propofol based on the Kataria model. Propofol target plasma concentration was 7 &mgr;g/ml for 15 min, followed by 1 &mgr;g/ml for 15 min or until signs of awakening, followed by 5 &mgr;g/ml for 15 min. Venous blood samples were taken 1, 2, 5, 10, and 15 min after each change in target. A classic pharmacokinetic-pharmacodynamic model was estimated, and the methodology of other studies was duplicated using pharmacokinetic models from the literature and (re-)estimating the pharmacodynamic models. Results:There is no clear relationship between pharmacokinetic precision and the pharmacodynamic objective function. Low pharmacodynamic objective function values are not associated with accurate estimation of the pharmacodynamic parameters when the pharmacokinetic model is taken from other sources. Conclusion:Minimization of the pharmacodynamic objective function does not select the most accurate pharmacokinetic model. Using population pharmacokinetic models from the literature instead of the ‘true’ pharmacokinetic model can lead to better predictions of bispectral index while incorrectly estimating the pharmacodynamic parameters.


Talanta | 2013

Development and validation of a fast and uniform approach to quantify β-lactam antibiotics in human plasma by solid phase extraction-liquid chromatography-electrospray-tandem mass spectrometry.

Pieter Colin; Lies De Bock; Huybrecht T'jollyn; Koen Boussery; Jan Van Bocxlaer

Monitoring of plasma antibiotic concentrations is necessary for individualization of antimicrobial chemotherapy dosing in special patient populations. One of these special populations of interest are the post-bariatric surgery patients. Until today, little is known on the effect of this procedure on drug disposition and efficacy. Therefore, close monitoring of antimicrobial plasma concentrations in these patients is warranted. A fast and uniform ultra-high-performance liquid chromatography (UPLC) method with tandem mass spectrometric detection (MS/MS) has been developed and qualified for the simultaneous quantification of β-lactam antibiotics in human plasma. Compounds included in this multi-component analysis are: amoxicillin, ampicillin, phenoxymethylpenicillin, piperacillin, cefuroxime, cefadroxil, flucloxacillin, meropenem, cefepime, ceftazidime, tazobactam, linezolid and cefazolin. After spiking of five different stable isotope labelled internal standards, plasma samples were prepared for UPLC-MS/MS analysis by mixed-mode solid phase extraction. The developed method was proven to be free of (relative) matrix effects and proved to be reliable for the quantification of 12 out of 13 β-lactam antibiotics. As a proof of concept the method has been applied to plasma samples obtained from a healthy volunteer treated with amoxicillin. The analytical method is suitable for use in a therapeutic drug monitoring setting, providing the clinician with reliable measurements on β-lactam antibiotic plasma concentrations in a timely manner.


Journal of Chromatography B | 2009

Pharmacokinetics of fluoroquinolones in critical care patients: A bio-analytical HPLC method for the simultaneous quantification of ofloxacin, ciprofloxacin and moxifloxacin in human plasma.

Julie De Smet; Koen Boussery; Kirsten Colpaert; Peter De Sutter; Peter De Paepe; Johan Decruyenaere; Jan Van Bocxlaer

A high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed and validated for the simultaneous quantification of ofloxacin, ciprofloxacin and moxifloxacin in human plasma. Sarafloxacin was used as internal standard. Chromatography was carried out using a Waters XBridge C(18) HPLC column and a gradient mobile phase consisting of CH(3)CN/MeOH/0.025M TBA.Cl/TFA (eluent A at 75/25/899/1 (v/v); eluent B at 150/50/799/1 (v/v); both at pH 3.5). Excitation/emission wavelengths were 279/442nm for ciprofloxacin and 290/500nm for ofloxacin, moxifloxacin and internal standard. Prior to chromatography, plasma samples were treated with acetonitrile for protein precipitation, followed by evaporation of the liquid layer and reconstitution in eluent A. The method was validated for the three fluoroquinolones over the clinically relevant concentration range from 0.02 to 7.50mug/ml. The method showed acceptable linearity with correlation coefficients, r(2)>0.995, as well as high precision (RSD% <7% in each case), accuracy (90.4-105.4%) and selectivity. The limit of quantification for the three fluoroquinolones was established at 0.02mug/ml. Ofloxacin, ciprofloxacin and moxifloxacin were extracted from plasma with a mean recovery of 95%, 86.4% and 94.2%, respectively. During validation, the concentration of the three fluoroquinolones was found to be stable after 3 freeze-thaw cycles and for at least 15h after extraction. This bio-analytical method was finally applied to the analysis of samples which have been obtained from patients, participating in a pharmacokinetic study on moxifloxacin.


Forensic Science International | 2001

Stability study of the designer drugs “MDA, MDMA and MDEA” in water, serum, whole blood, and urine under various storage temperatures

Karine M. Clauwaert; Jan Van Bocxlaer; André P. De Leenheer

A controlled study was undertaken to determine the stability of the designer drugs MDA, MDMA and MDEA in pooled serum, whole blood, water and urine samples over a period of 21 weeks. The concentrations of the individual designer drugs in the various matrices were monitored over time, in the dark at various temperatures (-20, 4 or 20 degrees C), for a low (+/- 6 ng/ml for water, serum and whole blood and +/- 150 ng/ml for urine) and a high concentration level (+/- 550 ng/ml for water, serum and whole blood and +/- 2500 ng/ml for urine). Compound concentrations were measured using a validated HPLC assay with fluorescence detection. Our study demonstrated no significant loss of the designer drugs in water and urine at any of the investigated temperatures for 21 weeks. The same results were observed in serum for up to 17 weeks, and up to 5 weeks in whole blood. After that time, the compounds could no longer be analyzed due to matrix degradation, especially in the low concentration samples that were stored at room temperature. This study demonstrates that the designer drugs, MDA, MDMA and MDEA are stable when stored at -20 degrees C for 21 weeks, even in haemolysed whole blood.


Peptides | 2010

Analytical characterization and comparison of the blood–brain barrier permeability of eight opioid peptides

Sylvia Van Dorpe; Antita Adriaens; Ingeborgh Polis; Kathelijne Peremans; Jan Van Bocxlaer; Bart De Spiegeleer

Opioid drugs, including the newly developed peptides, should penetrate the blood-brain barrier (BBB) for pain management activity. Although BBB transport is fragmentarily described for some mu-opioid peptides, a complete and comparative overview is currently lacking. In this study, the BBB transport of eight opioid peptides (EM-1, EM-2, CTAP, CTOP, DAMGO, dermorphin, TAPP and TAPS) is described and compared. In addition, the metabolic stability in plasma and brain was evaluated. The highest influx rate was obtained for dermorphin (K(in)=2.18 microl/(g x min)), followed by smaller rates for EM-1, EM-2 and TAPP (K(in)=1.06-1.14 microl/(g x min)). Negligible influx was observed for DAMGO, CTOP and TAPS (K(in)=0.18-0.40 microl/(g x min)) and no influx for CTAP. Capillary depletion revealed that all peptides reached brain parenchyma for over 75%. Efflux was shown for TAPP (t(1/2)=2.82 min) and to a lesser extent for EM-1, EM-2 and DAMGO (t(1/2)=10.66-21.98 min), while no significant efflux was observed for the other peptides. All peptides were stable in mouse plasma and brain, with generally higher stability in brain, except for EM-1 and EM-2 which showed plasma half-life stabilities of a few minutes only.


Photochemical and Photobiological Sciences | 2006

Flavin -induced photodecomposition of sulfur-containing amino acids is decisive in the formation of beer lightstruck flavor

Kevin Huvaere; Mogens L. Andersen; Michael Storme; Jan Van Bocxlaer; Leif H. Skibsted; Denis De Keukeleire

Photooxidation of sulfur-containing amino acids and derivatives readily occurs upon visible-light irradiation in the presence of flavins. The sulfur moiety seems pivotal for interaction, as was determined from kinetic analyses using laser flash photolysis spectroscopy. After photooxidation, the resulting radical intermediates were characterized by addition to a spin trap, followed by electron paramagnetic resonance spectroscopy and evaluation of the coupling constants. The presence of the proposed radical intermediates was strongly supported by the identification of the reaction products using mass spectrometry. Accordingly, feasible degradation pathways for various sulfur-containing amino acids and derivatives were proposed. It was finally proven that flavin-induced photoproduction of sulfhydryl radicals and recombination with a 3-methylbut-2-enyl radical, derived from the photodegradation of hop-derived isohumulones, are decisive in the formation of beer lightstruck flavor.

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