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Oral fluid (collected with the Intercept® device) and plasma samples were obtained from 139 individuals suspected of driving under the influence of drugs and analyzed for Δ9-tetrahydrocannabinol (THC), the major psychoactive constituent of cannabis, using a validated quantitative LC-MS-MS method. The first aim of the study was to investigate the correlation between the analytical data obtained in the plasma and oral fluid samples, to evaluate the use of oral fluid as a 'predictor' of actual cannabis influence. The results of the study indicated a good accuracy when comparing THC detection in oral fluid and plasma (84.9-95.7% depending on the cut-off used for plasma analysis). ROC curve analysis was subsequently used to determine the optimal cut-off value for THC in oral fluid with plasma as reference sample, in order to 'predict' a positive plasma result for THC. When using the LOQ of the method for plasma (0.5 ng/mL), the optimal cut-off was 1.2 ng/mL THC in oral fluid (sensitivity, 94.7%; specificity, 92.0%). When using the legal cut-off in Belgium for driving under the influence in plasma (2 ng/mL), an optimal cut-off value of 5.2 ng/mL THC in oral fluid (sensitivity, 91.6%; specificity, 88.6%) was observed. In the second part of the study, the performance of the on-site Dräger DrugTest® for the screening of THC in oral fluid during roadside controls was assessed by comparison with the corresponding LC-MS-MS results in plasma and oral fluid. Since the accuracy was always less than 66%, we do not recommend this Dräger DrugTest® system for the on-site screening of THC in oral fluid. © 2006 Elsevier Ireland Ltd. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

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A rapid and sensitive method for the analysis of Δ9- tetrahydrocannabinol (THC) in preserved oral fluid was developed and fully validated. Oral fluid was collected with the Intercept, a Food and Drug Administration (FDA) approved sampling device that is used on a large scale in the U.S. for workplace drug testing. The method comprised a simple liquid-liquid extraction with hexane, followed by liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Chromatographic separation was achieved using a XTerra MS C18 column, eluted isocratically with 1 mM ammonium formate-methanol (10:90, v/v). Selectivity of the method was achieved by a combination of retention time, and two precursor-product ion transitions. The use of the liquid-liquid extraction was demonstrated to be highly effective and led to significant decreases in the interferences present in the matrix. Validation of the method was performed using both 100 and 500 μL of oral fluid. The method was linear over the range investigated (0.5-100 ng/mL and 0.1-10 ng/mL when 100 and 500 μL, respectively, of oral fluid were used) with an excellent intra-assay and inter-assay precision (relative standard deviations, RSD <6%) for quality control samples spiked at a concentration of 2.5 and 25 ng/mL and 0.5 and 2.5 ng/mL, respectively. Limits of quantification were 0.5 and 0.1 ng/mL when using 100 and 500 μL, respectively. In contrast to existing GC-MS methods, no extensive sample clean-up and time-consuming derivatisation steps were needed. The method was subsequently applied to Intercept samples collected at the roadside and collected during a controlled study with cannabis. © 2005 Elsevier B.V. All rights reserved., SCOPUS: cp.j, info:eu-repo/semantics/published

The use of amphetamine and 'ecstasy' (MDMA) has increased exponentially in many European countries since the late nineties, leading to a rapid growth in the number of clinical and forensic analyses. Therefore, a rapid screening procedure for these substances in biological specimens has become an important part of routine toxicological analysis in forensic laboratories. The objective of this study was to evaluate the Cozart amphetamine enzyme-linked immunosorbent assay (ELISA) for the screening of plasma samples and oral fluid samples (collected with the Intercept device). Authentic plasma samples from drivers (n=360) were screened, using an 1:5-fold dilution. True positive, true negative, false positive and false negative results were determined relative to the in-house routine GC-MS analysis. Samples consisted of 144 amphetamine-only positives, 141MDMA/MDA-only positives, and 74 negatives when using the limit of quantitation as the cut-off level for confirmation (10 ng/mL). Using these results, receiver operating characteristic (ROC) curves were generated and optimal cut-off values for the screening assay were calculated. Analysis showed that the ELISA is able to predict the presence of either amphetamine or *MDMA/MDA (*MDMA as its metabolite MDA) in plasma samples with 98.3% sensitivity and 100% specificity at a cut-off value of 66.5 ng/mL d-amphetamine equivalents. A similar analysis was conducted on 216 oral fluid specimens collected from a controlled double blind study. Subjects received placebo or a high (100 mg) or low (75 mg) dose of MDMA. Oral fluid samples were collected at 1.5 and 5.5h after administration. Combined results of the analysis of the high and low dose oral fluid samples indicated a screening cut-off of 51 ng/mL d-amphetamine equivalents with both a sensitivity and specificity of 98.6% (using a LC-MS/MS confirmation cut-off of 10 ng/mL). In conclusion, these data indicate that the Cozart AMP EIA plates constitute a fast and accurate screening

A liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantification of 26 benzodiazepines and metabolites, zolpidem and zopiclone, in blood, urine, and hair. Drugs were extracted from all matrices by liquid-liquid extraction with 1-chlorobutane. Chromatography was achieved using a XTerra MS C18 column eluted with a mixture of methanol and formate buffer. Data were acquired using positive electrospray ionization and multiple reaction monitoring using one precursor ion/product ion transition per compound. Quantification was performed using 13 deuterated analogues. Further confirmation of the identity of the compounds was achieved through a second injection of positive samples, monitoring two transitions per compound. The limits of quantification for all benzodiazepines ranged from 1 to 2 ng/mL in blood, 10 to 25 ng/mL in urine, and 0.5 to 10 pg/mg in hair. Linearity was observed from the limit of quantification of each compound to 200 ng/mL, 1000 ng/mL, and 1000 pg/mg for blood, urine, and hair, respectively (r2 > 0.99). Precision for quality control samples, spiked at three concentrations, was calculated (CV < 20% in most cases). Extraction recoveries for the three matrices ranged from 25.1 to 103.8%, except for one compound (cloxazolam in urine). Ion suppression was studied for all matrices. The validated assay was applied to authentic blood, urine, and hair samples from forensic cases., SCOPUS: ar.j, info:eu-repo/semantics/published

In methanol intoxication, increased levels of the metabolite formate are associated with metabolic acidosis and an increased risk for ocular and neurological dysfunction. A simple method for plasma formate measurement by adaptation of a manual enzymatic assay to a Cobas Mira S analyzer is presented. Six microliters of sample is incubated for 5 min with buffer containing nicotinamide-adenine dinucleotide. Fifteen microliters of a suspension of formate dehydrogenase is then added. Absorbance at 340 nm is measured every 25 s. The NADH produced when formate is oxidized is stoichiometric to the amount of formate. The method is sensitive, reproducible, and specific and has a broad measurement range. The frozen reagents are stable for at least six months, so the described method can be applied to irregular and semi-urgent requests. A recent case is reported., Evaluation Studies, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

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During one year we have performed a qualitative urinary drug screening for patients attending the emergency care and with suspicion of drug abuse, in order to detect the following drug or its metabolites in urine: methadone (MTD), benzodiazepines (BZD), cocaïne (COC), amphetamine (AMP), opiates (OPI), barbiturates (BAR), tetrahydrocannabinoïds (THC), and tricyclics (TCA). The analyses were carried out at the laboratory by a restricted number of experienced technicians with the kit Triage-8 (Merck-Darmstadt). Positive results are easily identified by coloured bars on specific zones on the test cassette after a fast immunological reaction between urine and highly specific monoclonal antibodies. Of the 34000 patients having attended the emergency care during the year, 405 were screened: 290 were found positive (169 M and 121 F). The results were distributed as follows: 222 BZD, 80 MTD, 63 OPI, 53 BAR, 39 TCA, 59 THC, 18 AMP and 34 COC. Several drugs were often combined (up to 6 drugs). AMP was found preferentially for patients of less than 20 years, MTD, COC, THC, and TCA for patients between 20 and 60 years and BAR, OPI, and BZD in all the age classes but more frequently for patients from 20 to 60 years. For 87 patients, a request for screening blood by a HPLC/PDA method and urine by GC-MS was prescribed during the hours following the initial urinary screening. All the results were compared. They were concordant for 72 patients. In 6 cases, they were different but performed with a delay of more than 24H. In nine cases one result was different but on the other hand, for some samples, there was a presence of other drugs non detectable by our urinary screening: 4 times BZD (once in presence of pipamperone in the blood), 2 times MTD (once with propoxyphene and once with prothipendyl in the blood), once AMP and 2 times THC in urine comparisons (once with clomethiazol in blood and urine). The HPLC-PDA and GC-MS methods gave results for drugs that do not react in our urinary, SCOPUS: ar.j, info:eu-repo/semantics/published

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Gitaloxin is a digitalis glycoside used for the same indications as digoxin and digitoxin. The successful outcome for a 2 1/4 -year-old boy who accidentally ingested 3 mg of gitaloxin (100 times the normal therapeutic dose) is reported. At admission the child presented with irregular heart rhythm. He subsequently started vomiting, even after continuous gastric feeding. Only 48 h after ingestion of gitaloxin he became somnolent and developed bradyarrhythmia. The symptoms disappeared 96 h later; the bradyarrhythmia, however, (second-degree atrioventricular block) decreased progressively only after 120 h. The initial clinical presentation of gitaloxin poisoning may be misleading and careful observation in a pediatric intensive care unit is mandatory. A cross-reaction between the fluorescence polarization immunoassay for digitoxin and the radioimmunoassay for gitaloxin was found and was used as a helpful, but rough, estimate of the severity of gitaloxin poisoning, in the absence of a specific measurement of gitaloxin., SCOPUS: ar.j, info:eu-repo/semantics/published

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We investigated the possible origin of the spuriously high results observed with the Abbott TDx Immunoassay in the 1991 Belgian external quality assessment scheme for digoxin. The present work ascribes this discrepancy to a matrix effect induced by the addition of merthiolate as preservative to the control sainples. It consequently Stresses the importance of avoiding the use of this compound for preparing such samples. © 1994, Walter de Gruyter. All rights reserved., SCOPUS: no.j, info:eu-repo/semantics/published

The influence of diclofenac, given by continuous i.v. infusion starting preoperatively, on postoperative pain and inflammation was assessed in a double‐blind, randomized, placebo‐controlled study in 40 patients scheduled for major orthopedic surgery. Starting 30 min before induction the patients received either diclofenac (0.35 mg.kg‐1 bolus followed by a constant‐rate infusion of 90 μ.min‐1) or placebo for 24 h. The pain intensity (VAS) and the amount of rescue narcotic (piritramide on demand) were significantly lower in the diclofenac group from 4 and 6 h postsurgery, respectively, till end of infusion. Acute phase proteins used as inflammation markers (C‐reactive protein, α1‐chymotrypsin, α1‐acid glycoprotein, haptoglobin and coeruloplasmin) showed similar variations in both groups for 24 h. The diclofenac treatment had no influence on hematological and coagulation profiles, nor on muscle and liver enzymes in comparison with placebo. Both patients and observer rated the diclofenac treatment as significantly superior to the placebo treatment. © 1992 Acta Anaesthesiologica Scandinavica Fonden, SCOPUS: ar.j, info:eu-repo/semantics/published

1. The induction and inhibition of some biotransformation enzymes by valproate have been studied in hepatocytes isolated from rats treated with sodium valproate either i.p. or by subcutaneous implantation of osmotic pumps. 2. When valproate was given i.p. the cytochromes P-450 and b5, and aldrin epoxidase and glutathione S-transferase activities were significantly induced. 3. In contrast, valproate administered by osmotic pumps induced 7-ethoxycoumarin-O-deethylase activity, whereas aldrin expoxidase and glutathione S-transferase activities were significantly inhibited. At a valproate serum concentration of about 100 μg/ml for 2 weeks a significant induction of the cytochromes P-450 and b5 was observed. 4. Since there is a large difference between the half-lives of valproate in man and rodent, constant-rate delivery of valproate represents a better model for induction studies than i.p. injection. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted., SCOPUS: ar.j, info:eu-repo/semantics/published

The pharmacokinetics of lorazepam premedication were studied in 16 patients using two different formulations (intravenous and FDDF oral administrations). Arterial blood samples were taken at intervals for up to 600 min after administration of 4 mg of each formulation, and plasma lorazepam concentrations were determined by gas-chromatography with electron capture detection. Concentration-time data for individual subjects were analysed by model-independent methods. The derived pharmacokinetic parameters indicated a rapid distribution (median T( 1/2 ) λ1 i.v. = 15.2 min, median T( 1/2 ) λ1 oral = 31.6 min) into a steady-state volume of distribution approximating total body water, with long elimination half-life and a low clearance. V(dss) and clearance were similar with both treatments. The absorption of FDDF lorazepam was rapid in half of the patients and provided a high plasma concentration of lorazepam (C(max) = 61.8 ng ml-1) in a short time interval (T(max) = 58 min), but there were considerable inter-individual differences. This variability in absorption might explain why premedication with FDDF lorazepam is sometimes less effective than expected., SCOPUS: ar.j, info:eu-repo/semantics/published

A patient is reported presenting a cerebellar disorder developing about 5 weeks after acute exposure to an organophosphate insecticide. Initially no major cholinergic features were observed. The ataxia of delayed onset was not accompanied by clinical or electrophysiological signs of polyneuropathy. The possible pathogenetic mechanisms are reviewed and discussed. This case illustrates the need to closely monitor all patients intoxicated with such chemicals for at least 5 weeks. One should not only keep in mind the well-known late-onset polyneuropathy, but also the less frequent delayed central nervous system effects, even in the milder cases where initial signs of acetylcholine excess are only minimally present or lacking., SCOPUS: ar.j, info:eu-repo/semantics/published

A method is presented to determine the antibiotic amoxycillin and its inactive penicilloic acid metabolite in urine by the combination of two techniques., SCOPUS: ar.j, info:eu-repo/semantics/published