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Biomedical subjects

D de Boer

Publications and source records attributed to D de Boer.

At least 19 recordsLinked to original sources
PubMed2003

Seizure of illicitly produced para-fluorofentanyl: quantitative analysis of the content of capsules and tablets.

A gas chromatography/mass spectrometry (GC/MS) method for the quantification of para-fluorofentanyl (pFF) in powder and powdered samples was developed and validated. The method was applied on a seizure of capsules and tablets, that had been confiscated at an illicit production site in the Netherlands. The investigated capsules and tablets contained pFF in the range of 33.8-408.7 microg. As caffeine was detected as being an adulterant, a HPLC/UV method for the quantification of caffeine in capsules and tablets was also validated and applied. Caffeine was detected in the range of 25.6-108 mg per capsule or tablet. Based on an extrapolation of pharmacological and toxicological data of fentanyl, it can be argued that the highest detected single dose of pFF could be lethal, when administered orally. However, the large variability of the doses observed for pFF could mislead abusers, potentially leading to multiple doses and thus overdosing.

Caffeine↗
PubMed2002

Artifact formation due to ethyl thio-incorporation into silylated steroid structures as determined in doping analysis.

Trimethylsilylation of target substances in a mixture of N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide and ethanethiol is frequently applied for the application of gas chromatography-mass spectrometry (GC-MS) in steroid analysis. However, artifacts were formed when using this mixture to silylate the steroids androsterone and etiocholanolone obtained from a urine matrix. The artifacts were identified as ethyl thio-containing products of the respective trimethylsilyl derivatives. The conversion of the studied products increased slowly as a function of time, was dependent on the presence of the urine matrix and was significantly accelerated by adding diethyl disulfide to the reagent before incubation. Also ethyl thio-incorporation into testosterone and epitestosterone was established. A mechanism for ethyl thio-incorporation is proposed. The conversion achieved after 120-h sample storage at room temperature was insufficient to significantly influence the analysis of androsterone and etiocholanolone under the studied conditions. However, the results provide fundamental insight into the mechanism of silylation and the occurring side-reactions. Moreover, when investigating the formation of new metabolites, the ethyl thio-incorporation can lead to misinterpretation.

Artifacts↗
PubMed2001

Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market.

1-Aryl-piperazine compounds are, depending on their substituents, selective for certain serotonin receptors and together with their easy availability and their so-called legal status, this group of psychoactive compounds are potential designer drugs-of-abuse. Internet in that respect is an important source of information and distribution facilities. Because this development may have consequences for the interpretation of future clinical and forensic toxicological case studies, some analytical aspects of 1-benzyl-piperazine (BZP), 1-[4-methoxyphenyl]-piperazine (pMeOPP) and 1-[3-trifluoromethylphenyl]-piperazine (TFMPP) were studied. BZP was not detected by the AxSYM FPIA technology designed to determine amphetamine-like compounds, but had showed some cross reactivity with EMIT d.a.u.. The cross reactivities at 300 and 12,000ng/ml (RS)-amphetamine equivalents were 0.4 and 1.3%, respectively. Although BZP was not identified directly by the REMEDi HS Drug Profiling System, it can be detected by this HPLC/UV scanning system. Using GC/NPD without derivatisation, BZP, pMeOPP and TFMPP can be analysed for and applying GC/MS without or with acetylation or trifluoroacetylation, these compounds can be identified unambiguously. The usefulness of GC/NPD and GC/MS in this respect was demonstrated by the quantitative and qualitative analysis of the content of a capsule with the synthetic stimulant A2, which proved to contain 86.4mg of BZP.

Chromatography, High Pressure Liquid↗
PubMed2000

Evaluation of testosterone/epitestosterone ratio influential factors as determined in doping analysis.

The ratio of the concentration of testosterone glucuronide to the concentration of epitestosterone glucuronide (T/E ratio) as determined in urine is the most frequently used method to prove testosterone abuse by athletes. A T/E ratio higher than 6 has been considered as proof of abuse in the past; however, cases of naturally occurring higher T/E ratios have been described. Since the introduction of the T/E ratio in doping analysis, the parameters that may or may not influence the T/E ratio, possibly leading to false-positive results, have been debated. To achieve more insight on the influencing circumstances, an overview is given to obtain an objective view on the merits of the urinary T/E ratio. Relevant analytical aspects of the T/E ratio, potential parameters of endogenous and exogenous origins, as well as some alternative methods to determine testosterone abuse, such as the urinary testosterone/luteinizing hormone ratio, gas chromatography-combustion-isotope-ratio mass spectrometry, hair analysis, and high-performance liquid chromatography-mass spectrometry, are discussed.

Chromatography, High Pressure Liquid↗
PubMed1999

Para-methylthioamphetamine, a new amphetamine designer drug of abuse.

A case study is described of a patient who was intoxicated after the intake of so-called herbal stimulants. A visit to a physician after the intoxication prompted to this investigation and the case was examined for its direct cause. An interview with the patient revealed that the source of the herbal stimulants was a so-called 'S-5 tablet'. Information provided on the packings of the tablet only indicated the presence of natural alkaloids and vitamins. Toxicological analysis however proved that the 'S-5 tablet' contained para-methylthioamphetamine (MTA), mainly. MTA is a relative unknown amphetamine designer drug, which has only been studied as a model compound in some structure-activity relationship studies. The fact that MTA appeared in tablets was therefore completely unexpected. Not only the potential abuse of this new amphetamine designer drug is a serious matter of concern, but also the misleading information provided with the tablet.

Adult↗
PubMed1998

Differences in plasma concentrations of the D- and L-threo methylphenidate enantiomers in responding and non-responding children with attention-deficit hyperactivity disorder.

Children with attention-deficit hyperactivity disorder who are categorized as responders or non-responders to methylphenidate (MPH) on the basis of their electrophysiological P3 response in a selective attention task differ in metabolic patterns of the D- and L-threo MPH enantiomers. Non-responders showed significantly higher plasma concentrations of both D- and L-threo MPH enantiomers.

Analysis of Variance↗
PubMed1998

Survival after massive ecstasy overdose.

INTRODUCTION: The toxicity profile of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is well known. This designer drug is usually taken at "house parties" and may cause severe complications, sometimes leading to death, even when taken in relatively small units (1 or 2 tablets). Up to now, only a few cases of survival after ingestion of an overdose of Ecstasy have been described. In most cases the users developed hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, and renal failure. CASE REPORT: We describe a man who, after ingesting 50 tablets of Ecstasy (in combination with oxazepam and alcohol) at home, recovered within 2 days. Presenting features were unconsciousness, apnea, and convulsions. It is suggested that in most cases severe 3,4-methylenedioxymethamphetamine toxicity results from an interaction between direct pharmacological effects of the drug and the prevailing environmental conditions (high ambient temperature, dancing in trance, little fluid intake).

Adult↗
PubMed1997

Gas chromatographic/mass spectrometric assay for profiling the enantiomers of 3,4-methylenedioxymethamphetamine and its chiral metabolites using positive chemical ionization ion trap mass spectrometry.

A qualitative GC/MS profile was obtained and its mass spectrometric features characterized for the analysis of the enantiomers of (RS)-3,4-methylenedioxymethamphetamine (MDMA) and its metabolites (RS)-3,4-methylenedioxyamphetamine (MDA), (RS)-4-hydroxy-3-methoxymethamphetamine (HMMA) and (RS)-4-hydroxy-3-methoxyamphetamine (HMA). A chiral derivatization method was selected to obtain the diastereomers required for the separation of the respective enantiomers with a non-chiral GC stationary phase. The selected derivatization consisted of a reaction with N-heptafluorobutyryl-(S)-prolyl chloride combined with a consecutive reaction with N-methyl-N-trimethylsilyltrifluoroacetamide, resulting in N-[heptafluorobutyryl-(S)-prolyl]-O-trimethylsilyl derivatives. Detection was carried out with electron ionization and positive chemical ionization (PCI) ion trap mass spectrometry. Mass spectra of the derivatives of reference standards of the compounds of interest obtained with PCI demonstrated that this method simultaneously induces proton and charge-transfer reactions in the ion trap. The advantage is that high mass information is provided while some fragmentation remains to elucidate structural details. Subsequently, in three urine samples obtained from different and unrelated MDMA intoxications, the enantiomers of MDMA and MDA were identified. In some urine samples also HMMA and/or HMA were found. In addition to these compounds, an unexpected compound and/or additional chiral metabolite, N-hydroxy-(RS)-3,4-methylenedioxyamphetamine, was identified in two out of three urine samples. Preliminary results also indicated an enantioselective metabolism in the N-demethylation pathway for MDMA in humans.

Biotransformation↗
PubMed1996

Enantioselective quantitation of (R)- and (S)-alprenolol by gas chromatography-mass spectrometry in human saliva an plasma.

An enantioselective gas chromatographic-mass spectrometric assay is developed for alprenolol and its metabolite, 4-hydroxy-alprenolol, in saliva and plasma. The procedure is based on a two-step derivatization technique with N-heptafluorobutyryl-l-prolylchloride and N-methyl-N-trimethylsilyl-trifluoroacetamide, followed by a gas chromatographic separation with mass spectrometric detection of the diastereomeric derivatives. A selected ion chromatogram extracted from full scan data shows that the respective enantiomers of alprenolol, 4-hydroxy-alprenolol, and the internal standard (ions at m/z 481) are well-separated in saliva and plasma. Linear and reproducible calibration curves are obtained over the concentration ranges 1.67-13.33 ng/mL and 2.50-20.00 ng/mL enantiomer in saliva and plasma, respectively. The performance of the method for alprenolol, in terms of accuracy and precision, fits well within the generally accepted criteria for validation. The enantioselective assay is successfully used in a study involving a single oral dose of alprenolol administered to two healthy volunteers. Stereoselective differences are observed in the saliva and plasma concentrations following an oral dose of 50 mg (R,S)-alprenolol hydrochloride.

Adult↗
PubMed1995

Evaluation of the Salivette as sampling device for monitoring beta-adrenoceptor blocking drugs in saliva.

The Salivette was evaluated with a range of racemic beta-adrenoceptor blocking drugs with different lipophilicity. Recovery from the Salivette appeared to be independent of the stereochemical configuration of the drugs but a significant loss of drug due to the Salivette was observed for all tested drugs. The performance of the method, in terms of accuracy and precision, fitted well within the generally accepted criteria for validation, except near the limit of quantification. The Salivette is successfully used for quantitating salivary beta-blocking drugs.

Adrenergic beta-Antagonists↗
PubMed1995

The secretion of propranolol enantiomers in human saliva: evidence for active transport?

To study the possible transport routes which may lead to the presence of a drug in saliva, the concentration-time curves of the separate enantiomers of propranolol were measured in human saliva and plasma after oral administration of 10 mg of propranolol hydrochloride. Saliva samples were taken with the Salivette device. Plasma and saliva concentrations of the enantiomers of propranolol were determined by HPLC with fluorescence detection. The transport of propranolol from plasma to the salivary gland appears to be not stereospecific and not saturable. Therefore, there is no indication that the transport of propranolol to the salivary gland is active. The concentrations of both enantiomers of propranolol in saliva, however, were higher than those of both enantiomers in venous plasma. In the past this phenomenon was interpreted as an indication of active transport, but it could be explained by the fact that salivary concentration more closely reflects the central compartment than that of peripheral venous blood.

Adrenergic beta-Antagonists↗
PubMed1992

The methyl-5 alpha-dihydrotestosterones mesterolone and drostanolone; gas chromatographic/mass spectrometric characterization of the urinary metabolites.

Before including the detection of the methyl-5 alpha-dihydrotestosterones mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) and drostanolone (2 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) in doping control procedures, their urinary metabolites were characterized by gas chromatography/mass spectrometry. Several metabolites were found after enzymatic hydrolysis and conversion of the respective metabolites to their trimethylsilyl-enol-trimethylsilyl ether derivatives. The major metabolites of mesterolone and drostanolone were identified as 1 alpha-methyl-androsterone and 2 alpha-methyl-androsterone, respectively. The parent compounds and the intermediate 3 alpha,17 beta-dihydroxysteroid metabolites were detected as well. The reduction into the corresponding 3 beta-hydroxysteroids was a minor metabolic pathway. All metabolites were found to be conjugated to glucuronic acid.

Androstanols↗
PubMed1991

The analysis of trenbolone and the human urinary metabolites of trenbolone acetate by gas chromatography/mass spectrometry and gas chromatography/tandem mass spectrometry.

The electron impact mass spectrometric properties of trimethylsilyl ether and fluoroacyl ester derivatives of trenbolone, combined or not combined with a methoxime group, are presented. Some derivatization problems were observed and were due to the formation of enol derivatives at the 3C-position in several tautomeric forms, which in their turn were not stable and lost two or four hydrogens under the conditions studied. The enolization could be minimized by carefully selecting the reaction conditions or could be prevented by the introduction of a methoxime group at the 3C-position. The limits of detection and identification of the methoxime heptafluorobutyryl ester and the methoxime trimethylsilyl ether derivative of trenbolone were determined using a mass selective detector in the electron impact mode and a triple-stage quadrupole in the methane positive chemical ionization mode. Selected reaction monitoring in tandem mass spectrometry did not improve the limit of detection, but because of the gain in selectivity did improve the limit of identification. The glucuronides of trenbolone and epitrenbolone could be identified in three urine specimens out of 200 samples in routine doping control.

Fluoroacetates↗
PubMed1991

Protein targeting towards the thylakoid lumen of chloroplasts: proper localization of fusion proteins is only observed in vivo.

Routeing of fusion proteins to the thylakoid lumen of the chloroplast was compared in vitro and in vivo. The Escherichia coli protein beta-lactamase was used as a passenger to study this intraorganellar sorting process. The first step, translocation of beta-lactamase into the chloroplast stroma, occurs properly both in vitro and in vivo and is dependent on the presence of a transit peptide in the protein construct. The second step, targeting towards the thylakoid lumen, is more complicated as was also observed previously when other passenger proteins were used. In vitro, the presence of a thylakoid transfer domain is not enough for routeing and proper processing. Only when the complete thylakoid lumen precursor plastocyanin was fused to beta-lactamase was the fusion protein processed adequately, but routeing was still incomplete. However, in vivo, the information present in the thylakoid transfer domain was the only requirement for proper transport towards the thylakoid lumen. These data show that in vivo, the only requirement for targeting of passenger proteins towards the thylakoid lumen is the presence of a transit peptide and a thylakoid transfer domain. Furthermore, we demonstrate that the in vitro import system does not necessarily reflect the in vivo situation with respect to intraorganellar sorting.

Amino Acid Sequence↗
PubMed1991

Doping control of testosterone and human chorionic gonadotrophin: a case study.

Doping control for testosterone and human Chorionic Gonadotrophin (hCG) requires special attention as a difference must be made between the endogenous and exogenous origin of both substances. The detection of exogenous testosterone is based on the ratio of testosterone- to epitestosterone-glucuronide (T/E) in urine. The problems with this ratio are discussed. For hCG analysis in urine the utilization of sandwich-type hCG specific assays instead of hCG/hCG beta competitive assays is recommended. A case study in which an athlete self-administered testosterone and hCG before a competition is described. The T/E ratio and hCG concentration in urine were followed during this period of self-administration. The results demonstrate the relevance of the T/E ratio and of the selected hCG assay. The ratio of testosterone to human Luteinizing Hormone (T/hLH) in serum also indicated the use of hormones. Although the athlete's urine was negative for exogenous testosterone directly after competition, he would have been found positive for hCG.

Chorionic Gonadotropin↗
PubMed1990

Mass spectrometric characterization of different norandrosterone derivatives by low-cost mass spectrometric detectors using electron ionization and chemical ionization.

The abuse of nortestosterone in sport is an important problem in doping-control analysis. In order to detect the main urinary metabolite of nortestosterone, norandrosterone (NA), sensitive and specific methodology is necessary. In this context the use of a low-cost mass spectrometric detector such as the Finnigan MAT ion-trap detector (ITD) was studied. The electron ionization (EI) and positive-ion chemical ionization (PICI) mass spectra of the methoxime-trimethylsilyl, trimethylsilyl-enol trimethylsilyl ether and pentafluoropropionic ester derivatives of NA are described. The limits of detection of these derivatives are compared with those obtained by the Hewlett-Packard mass selective detector (MSD), another low-cost mass spectrometric detector and operating only in the EI mode. For the derivatives of the reference standard of NA the ITD has in the EI mode the same limit of detection, in the range of 0.5 to 1 ng injected on the column, as the MSD. However, under these conditions the ITD provides more spectrometric information, because it gives full scan data. Moreover, with the same or even improved limits of detection the ITD can operate in the PICI mode. On the other hand, for the analysis of NA isolated from urine samples, the performance of the MSD was better than that of the ITD. The ion trapping technique is probably limited when the chemical background is high.

Anabolic Agents↗
PubMed1989

Import of proteins into the chloroplast lumen.

Plastocyanin is a nuclear-encoded protein that is functional in the thylakoid lumen of the chloroplast. It is synthesized in the cytoplasm as a precursor with an N-terminal transit peptide of 66 amino acids. Its transport route involves two steps, import into the chloroplasts and subsequent routing over the thylakoid membrane into the lumen. Concomitant with the transport, the transit peptide is removed in two successive steps. The transit peptide consists of two functionally different domains. In this study we examine to what extent each domain is involved in import and routing and how far these two processes are linked. For this purpose we made deletions in the N-terminal and C-terminal part of the transit peptide and fusion proteins which only contain one of these parts. The results show that the N-terminal part of the transit peptide is responsible for import into the chloroplast. The N-terminal 43 amino acids are sufficient to direct other proteins into the stroma. The C-terminal part of the transit peptide is a prerequisite for routing inside the chloroplast but not for import. When deletions are made in this part, the transport of plastocyanin stops after import and the intermediate accumulates in the stroma or on the outside of the thylakoids. Transgenic tomato plants that constitutively express a foreign plastocyanin gene were used to study protein transport in different tissues. Normally, expression of endogenous plastocyanin genes in plants is restricted to photosynthetic tissues only. However, in the transgenic plants this foreign plastocyanin protein is found in all tissues examined. The protein is transported into the local plastids of these tissues and it is processed to the mature size. We conclude that plastids of developmentally different tissues are capable of importing precursor proteins that are normally not found in these tissues. Most likely such plastids, though functionally and morphologically differentiated, have similar or identical protein import mechanisms when compared to the chloroplasts in green tissue. The precursor of ferredoxin was expressed in Escherichia coli. Surprisingly the precursor interacts with the cytoplasmic membrane and is translocated across this membrane. The unprocessed precursor accumulates in the periplasm.

Amino Acid Sequence↗