Biomedical subjects

F T Delbeke

Publications and source records attributed to F T Delbeke.

At least 37 records · Page 2Linked to original sources

PubMed2002

Detection of inhaled salbutamol in equine urine by ELISA and GC/MS2.

Salbutamol is a beta-adrenergic agonist that is used in the treatment of asthma in humans and chronic obstructive pulmonary disease in horses. Because of its stimulating and growth promoting properties, it is prohibited by horse racing authorities. Recently a number of adapters (eg Equinehaler) have been designed, allowing the use of metered dose inhalers (MDI) approved for human use. However, information on detection times of salbutamol after administration of salbutamol in therapeutic doses by inhalation is lacking. In this study, 2 mg salbutamol (Ventolin) was administered to four standardbred mares via an MDI with an Equinehaler and urine was collected during 48 h. Quantification of salbutamol in horse urine was done via an overnight beta-agonist ELISA kit. Salbutamol was detected between 1 and 48 h post-administration. Relatively large interindividual variations in the total amount excreted during the first 12 h were noticed. The maximum urinary concentrations varied between 4.6 and 8.1 ng/mL. The total amount excreted within the first 12 h varied between 0.2 and 0.7% of the administered dose. For confirmatory analysis in doping control, a GC/MS(2) method was developed and validated. Analysis was performed on an ion trap instrument after solid phase extraction. The limit of detection was 0.25 ng/mL and was lower than in previously reported methods in human urine.

Adrenergic beta-Agonists↗

PubMed2002

Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography-tandem mass spectrometry.

A fast and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the screening of 18 diuretics and probenecid in human urine is presented. Analyses were performed on a LCQ-Deca instrument equipped with ESI-interface using scan by scan polarity changing. All diuretics and probenecid were separated in less than 20 min after liquid-liquid extraction with ethyl acetate. The LOD for all substances was 100 ng/mL or better. The method was applied to detect diuretics after the oral administration of several drugs including hydrochlorothiazide, bumetanide, spironolactone, furosemide, amiloride, triamterene, chlortalidone and epithizide. All diuretics could be detected for periods up to 96 h after the intake of therapeutic amounts.

Chromatography, Liquid↗

PubMed2002

Quantitative detection of salmeterol after inhalation in equine urine by liquid chromatography/tandem mass spectrometry.

A sensitive, accurate and precise liquid chromatography/tandem mass spectrometry (LC/MS(2)) method was developed for the quantification of salmeterol in the urine of horses. The method consists of a liquid-liquid extraction with tert-butylmethyl ether and isopropanol at pH 12 after enzymatic hydrolysis. The extracts are analysed using an LC/MS system equipped with an electrospray ionisation (ESI) probe. Method validation showed excellent linearity, specificity, accuracy, precision and intra-laboratory repeatability and reproducibility. The limit of quantitative detection was 0.25 ng/mL and the limit of detection was 0.125 ng/mL. The excretion profile was determined after administration of 500 microg salmeterol (Serevent) to four standard-bred mares via a metered dose inhaler (MDI) with an Equinehaler adapter. Salmeterol was detected from 1 h until 12 h post-administration. Maximum urinary concentrations varied between 2.3 and 14.9 ng/mL.

Administration, Inhalation↗

PubMed2001

Simultaneous quantitation of ephedrines in urine by gas chromatography-nitrogen-phosphorus detection for doping control purposes.

A gas chromatographic method for the simultaneous quantitation of ephedrine, pseudoephedrine, norephedrine (phenylpropanolamine), norpseudoephedrine (cathine) and methylephedrine in urine is described. The method consists of a liquid-liquid extraction with tert.-butyl methyl ether at pH 14. The extracts are analysed on a GC system equipped with an Rtx-5 Amine column and a nitrogen-phosphorus detector. Method validation shows excellent separation, linearity, specificity, accuracy, precision, intra-laboratory repeatability and reproducibility, making the method especially suitable for quantitation of ephedrines in urine samples for doping control purposes. A statistical analysis on the abuse of the different ephedrines in urine from athletes controlled in the Flemish doping control laboratory during the period 1993-2000 is included.

Calibration↗

PubMed2001

Detection and determination of anabolic steroids in nutritional supplements.

A method is described for the determination of anabolic steroids including testosterone, 19-nor-4-androstene-3,17-dione, 4-androstene-3,17-dione and nandrolone in food supplements. Initial clean-up is done by HPLC followed by determination with GC/MS. A 'contaminated' food supplement was analysed and appeared to contain 19-nor-4-androstene-3,17-dione and 4-androstene-3,17-dione. One capsule of this nutritional supplement was ingested by five male volunteers. Urine samples were collected and analysed by GC/MS and GC/MS-MS. Neither the ratio testosterone/epitestosterone, nor the ratio androstenedione/epitestosterone increased significantly. Concentrations above 2 ng/ml for norandrosterone, the major metabolite of nandrolone, were detected until 48-144 h after ingestion of the food supplement.

Anabolic Agents↗

PubMed2001

Endogenous origin of norandrosterone in female urine: indirect evidence for the production of 19-norsteroids as by-products in the conversion from androgen to estrogen.

Recently the use of high resolution mass spectrometry or tandem mass spectrometry has enabled the detection of low amounts of anabolic steroids. As a consequence, the post-administration detection time of these drugs has been extended. Recent investigations have shown that norandrosterone, previously unequivocally regarded as evidence of nandrolone administration, might be an endogenous steroid present in small amounts in urine of humans. In this study, very low concentrations (<1 ng/ml) of norandrosterone in urine of a female athlete were detected using tandem mass spectrometry. The presence of norandrosterone was strongly correlated with high plasma 17beta-estradiol levels during the menstrual cycle. Analysis of urine samples from pregnant women supports the hypothesis of formation of precursors for urinary 19-norandrosterone during aromatization of androgens to estrogens. The detection of low urinary concentrations of norandrosterone (0.2-0.5 ng/ml) in samples after strenuous exercise could be regarded as an additional evidence for the existence of such a pathway.

Androgens↗

PubMed1998

Detection of human chorionic gonadotrophin misuse in sports.

The peptide hormone human chorionic gonadotrophin (hCG) was measured in the urine of 5663 male athletes collected for doping analysis in Flanders during the period 1993-1996. Using the Abbott IMx hCG procedure, the free and whole molecule associated beta-subunit of human chorionic gonadotrophin was determined. Statistical evaluation of the data results in a far outside value of 2.28 mIU/ml. The decision limit, i.e. the concentration at which a sportsman will be considered positive, is set at 5 mIU/ml to ensure with the greatest possible degree of certainty that no false positive results are reported.

Adolescent↗

PubMed1997

Disposition of human drug preparations in the horse. VI. Tiaprofenic acid.

Urinary and plasma concentrations of the nonsteroidal anti-inflammatory drug tiaprofenic acid were determined following oral and intramuscular administration of a dose of 1 g to five fasted horses. Quantitation was performed by high-performance liquid chromatography (HPLC). The limit of quantitation (LOQ) was 0.1 microg/ml and 0.5 microg/ml in 2 ml plasma and 1 ml urine, respectively. Assay precision and extraction recovery were between acceptable values. Tiaprofenic acid pharmacokinetics were described by non-compartment analysis of the data. Absorption was faster after oral administration as maximum plasma concentrations (oral: 6.0+/-3.3 microg/ml; intramuscular: 6.6+/-2.5 microg/ml) were obtained after 1 h (oral) compared to 1.6+/-0.4 h (intramuscular) post dosage. Plasma binding (66+/-3%) was lower than measured in other species. Tiaprofenic acid was detected in urine for at least 24 h. The percentage of the parent drug excreted in the first 12 h after oral and intramuscular administration was 38+/-6% and 34+/-5%, respectively.

Absorption↗

PubMed1996

Threshold level for theophylline in doping analysis.

HPLC in the reversed-phase mode is used to assay methylxanthines including theobromine, paraxanthine, theophylline and caffeine in urine. The calibration graphs show good linearity in the concentration range 0-10 micrograms/ml. The limit for accurate quantitation of theophylline was 0.25 microgram/ml. Between 6 and 20% of the parent drug is recovered in urine (0-12 h) after the oral administration of sustained release preparations containing 150 and 250 mg theophylline to four volunteers. Theophylline levels above 0.25 microgram/ml were found in 1539 out of 3885 urine samples collected from athletes during unannounced doping control in Flanders. Statistical evaluation of the results gives a far outside value [75th percentile+(3 x interquartile range)] of 2.25 micrograms/ml. The ratio theophylline paraxanthine (TP/PX) as an indicator for the non-dietary intake of theophylline seems to be more reliable. The far outside ratio was 0.20. To ensure with the greatest possible degree of certainty that no false-positive result is reported, decision limits of 5 micrograms/ml and 0.50, for theophylline and the ratio TP/PX respectively, are proposed.

Caffeine↗

PubMed1996

Doping in cyclism: results of unannounced controls in Flanders (1987-1994).

Unannounced doping control in cyclism, the most favourite sport in Flanders, resulted in 7.8% positive cases in 4374 analysed samples during the period 1987-1994. Ephedrines, amphetamine and nandrolone were frequently misused and polydrug abuse including ephedrines and amphetamine seemed to be very popular. The abuse of methamphetamine, methylphenidate and pemoline, formerly favourite drugs in cyclists is decreasing while prolintane, codeine and the anabolic steroids nandrolone and testosterone were more frequently detected. The misuse of forbidden substances by athletes competing in the official Belgian Cyclist Federation and in amateur federations was 5.8% and 8.9%, respectively. Several cyclists however attempted to circumvent doping control.

Belgium↗

PubMed1995

Disposition of human drug preparations in the horse. IV. Orally administered fenoprofen.

Plasma and urinary concentrations of the non-steroidal anti-inflammatory drug fenoprofen were determined by a high-performance liquid chromatographic procedure following oral administration of a dose of 3 g to fed and fasted horses. In plasma, fenoprofen was present in detectable concentrations for 6-12 h. Free access to hay significantly reduced the peak plasma concentration and bioavailability of fenoprofen, and large interindividual differences in absorption and elimination pattern occurred. In fasted horses, fenoprofen was rapidly absorbed with a mean half-life of 0.10 h. Maximum concentrations were found 0.63 +/- 0.21 h after dosing. The elimination half-life was 0.9 h. As early as 1 h after dosage, fenoprofen could be detected in hydrolysed and unhydrolysed urine, and remained detectable up to 48 h. The maximum excretion rate and peak concentration occurred 2 h after administration, irrespective of the feeding schedule. In fed horses, a second maximum occurred after 9 h. The percentage of the dose excreted as unchanged fenoprofen in 12 h was 13.0 +/- 6.8%. A recovery of 21.9 +/- 7.4% and 42.2 +/- 7.0% of the dose was obtained after enzymatic and alkaline hydrolysis, respectively. At least three hydroxylated metabolites were detected in hydrolysed urine.

Administration, Oral↗

PubMed1995

The abuse of doping agents in competing body builders in Flanders (1988-1993).

Analytical findings of unannounced doping control in body builders in Flanders during 1988-1993 are reported. In some federations between 38 and 58% of the controlled athletes were found positive during this period. The results show that there was no fall in drug abuse over this period and steroids were taken even by body builders associated with an organisation against the use of anabolic steroids. In 1988 and 1989 popular anabolic steroids were nandrolone and testosterone. From 1990 on, a wide range of mostly injectable steroids including nandrolone, metenolone, drostanolone and testosterone were administered. Polydrug abuse including several anabolics in combination with stimulants and diuretics was also widespread. The beta agonist clenbuterol was detected in several urine samples taken in 1991, one year before its appearance in other sports.

Belgium↗

PubMed1994

Disposition of human drug preparations in the horse. III. Orally administered alclofenac.

Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1 = 0.05 +/- 0.06 h-1 and ka2 = 0.06 +/- 0.01 h-1. Alclofenac half-lives t1/2 alpha and t1/2 beta were 1.0 +/- 0.8 h and 6.9 +/- 1.5 h, respectively. Maximal concentrations (38.9 +/- 16.2 micrograms/ml) were obtained after 8.5 +/- 2.4 h. Alclofenac was detected in urine for at least 48 h after dosing. The percentage of the dose excreted as unchanged alclofenac in 12 h was very low (0.68 +/- 0.19%), total (free+conjugated) alclofenac accounted for 2.16 +/- 0.55% of the dose.

Administration, Oral↗

PubMed1993

Determination of alclofenac in equine plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method to measure plasma and urinary alclofenac levels in equine biofluids is described. Isolation of the drug from plasma is achieved using liquid-liquid extraction with diethyl ether. Reversed-phase C18 solid phase extraction is used for the extraction of free and conjugated alclofenac from urine. The reproducibility and accuracy of the method were well within acceptable limits over the concentration ranges 0-10 and 0-20 micrograms/ml, respectively, for plasma and urine. Starting with 2 ml of plasma, a concentration of 0.1 microgram/ml could easily be measured; the limit of quantification in urine (0.5 ml) was 1 microgram/ml. Hydrolysis of urine with strong alkali resulted in the decomposition of alclofenac. A pharmacokinetic profile of alclofenac in the horse is shown.

Animals↗

PubMed1993

ELISA screening with GC-MS confirmation of the tranquilizer chlorprothixene administered in subtherapeutic doses to horses.

A commercially available generic promazine ELISA kit is available which shows cross-reactivity for the tranquilizer chlorprothixene (CPT). The ELISA test readily detects the presence of CPT or its metabolites in equine urine for up to 24 h after the i.v. and i.m. administration of sub-therapeutic doses (4.5 mg) to three horses. Maximum concentrations (CPT equivalents) are obtained 2 h after i.v. dosing. No distinct concentration peak values are observed after i.m. administration. Following solid-phase extraction, confirmation of CPT and its metabolites by electron impact mass spectrometry after sub-therapeutic administration is not successful. The use of chemical ionization mass spectrometry however revealed the presence of at least four metabolites including; chlorprothixene sulphoxide, hydroxylated chlorprothixene and hydroxylated chlorprothixene sulphoxide.

Animals↗

PubMed1993

The disposition of suxibuzone in the horse.

A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a beta half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ were detected in plasma and urine after p.o. SXB administration. Peak plasma PBZ concentrations (8.8 +/- 3.0 micrograms/ml) occurred 6 h after oral dosing and the terminal exponential constant was 0.11 +/- 0.01 h-1. Phenylbutazone and oxyphenbutazone were detectable in urine (> 1 microgram/ml) for at least 36 h, after p.o. administration. SXB was not hydrolyzed in vitro by horse plasma. Equine liver homogenates however appeared to have a very high capacity for hydrolysing SXB, indicating that first-pass effect could be responsible for the rapid disappearance of this NSAID in the horse.

Administration, Oral↗

PubMed1993

The intramuscular bioavailability of a phenylbutazone preparation in the horse.

The plasma concentrations of phenylbutazone (PBZ) and its major metabolites, oxyphenbutazone (OPBZ) and gamma-OH-phenylbutazone (OHPBZ) were determined for up to 72 h in six horses, following intravenous (i.v.) and intramuscular (i.m.) administration of 4 g phenylbutazone, 20 ml Phenylarthrite Ventoquinol (Vetoquinol Spécialités Pharmaceutiques Vétérinaires, Magny-Vernois, 70200 Lure, France). After i.v. dosing the plasma disposition was best described by a two-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 48 h, respectively. After 36 h the OPBZ concentrations exceeded plasma PBZ concentrations. The plasma disposition following i.m. injection could be described by a one-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 36 h, respectively. Only after 72 h was the concentration of OPBZ in plasma higher than the concentration of PBZ. The mean i.m. bioavailability of phenylbutazone was calculated to be 91.7 +/- 10.1%.

Animals↗

PubMed1992

Disposition of human drug preparations in the horse. II. Orally administered fencamfamine.

A gas chromatographic method to measure urinary levels of the central nervous system stimulant fencamfamine and some of its metabolites is described. When 100 mg fencamfamine was given orally to four horses the parent drug could not be detected in the urine. After enzymatic hydrolysis of the urine the major human metabolite, N-desethylated fencamfamine, only accounted for 1% of the dose in 12 h. The major equine metabolites were conjugated parahydroxylated compounds representing 18% of the dose. With regard to horse doping control and analysis, the injudicious use of human doping routine methods for the detection of fencamfamine in equine urine could lead to false negative results.

Administration, Oral↗