Abstract:
:1-(4-Methylphenyl)-2-pyrrolidin-1-ylhexan-1-one (4'-methyl-alpha-pyrrolidinohexanophenone, MPHP) is a new designer drug that appeared on the illicit drug market. It is mainly metabolized to 4'-hydroxymethyl-alpha-pyrrolidinohexanophenone (HO-MPHP) followed by oxidation to the respective carboxylic acid. For studies on the quantitative involvement of human cytochrome P450 (CYP) isoenzymes in the initial hydroxylation, a reference standard of HO-MPHP was needed. Therefore, the aim of this study was to synthesize this metabolite using a biotechnological approach. MPHP.HNO(3) (250 micromol) was incubated with 1 L culture of the fission yeast (Schizosaccharomyces pombe) strain CAD64 heterologously co-expressing human CYP reductase and CYP2D6. After centrifugation, the product was isolated from the incubation supernatants by solid-phase extraction. Further product cleanup was achieved by semi-preparative high-performance liquid chromatography (HPLC). After extraction of HO-MPHP from the respective eluent fractions, it was precipitated as its hydrochloric salt. The final product HO-MPHP.HCl was obtained in a yield of 138 micromol (43 mg, 55%). Its identity was confirmed by full scan gas chromatography-mass spectrometry (after trimethylsilylation), (1)H-NMR, and (13)C-NMR. The product purity as estimated from HPLC-ultraviolet analysis was greater than 99%. The described biotechnological approach proved to be a versatile alternative to the chemical synthesis of HO-MPHP.
journal_name
J Anal Toxicoljournal_title
Journal of analytical toxicologyauthors
Peters FT,Dragan CA,Kauffels A,Schwaninger AE,Zapp J,Bureik M,Maurer HHdoi
10.1093/jat/33.4.190subject
Has Abstractpub_date
2009-05-01 00:00:00pages
190-7issue
4eissn
0146-4760issn
1945-2403journal_volume
33pub_type
杂志文章abstract::Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former s...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/bku109
更新日期:2015-01-01 00:00:00
abstract::Two cases of overdose due to ingestion of trazodone are described. In one case, blood collected several hours following ingestion of an estimated 4 or more grams contained a trazodone concentration of 25.7 mg/L. Recovery was uneventful. The second case did not survive and death was attributed to the ingestion of multi...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/8.2.91
更新日期:1984-03-01 00:00:00
abstract::Due to the lack of certified reference material, a reliable quantification in complex postmortem matrices can only be performed either by the addition of isotope-labelled standards or by the standard addition method. Although standard addition is a basic quantification procedure, its practical implementation is challe...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/bkv078
更新日期:2015-11-01 00:00:00
abstract::Dried blood spots (DBS) on filter paper have been used in human medicine since the 1960s, predominantly for screening in-borne metabolic disorders and more recently, for toxicology. Despite its 50-year existence, this technology has not been adopted by veterinarians for routine diagnoses and research. We have validate...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/bkt048
更新日期:2013-09-01 00:00:00
abstract::An analytical method for determining exposure to 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD) has been enhanced. The method is based on the cleavage of adducted HD (protein-hydroxyethylthioethyl esters) to produce thiodiglycol. Following cleavage, a deuterated internal standard is added, and the analytes are extr...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/32.1.31
更新日期:2008-01-01 00:00:00
abstract::Comprehensive investigation is necessary for determining the cause of death in cases with positive drug screens. We investigated the case of a male who reportedly expired from an acute asthma attack. He had limited access to both therapeutic drugs and drugs of abuse because he was a state prisoner. His autopsy was rem...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/19.6.522
更新日期:1995-10-01 00:00:00
abstract::An improved method for the simultaneous determination of cocaine and its metabolites, benzoylecgonine (BE), norcocaine, and ecgoninemethylester (EME), in rat plasma and urine is described. Following derivatization of EME to p-fluorococaine, chromatography was performed on two high-performance liquid chromatography (HP...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/24.6.438
更新日期:2000-09-01 00:00:00
abstract::Doxepin is a tricyclic antidepressant that is widely prescribed for the treatment of mild depression. In this study, hair samples collected from a patient receiving 25 mg of doxepin daily were analyzed. Doxepin was administered to the patient for 4 months (June 15 to October 15, 1996). Five hair samples were collected...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/22.6.531
更新日期:1998-10-01 00:00:00
abstract::3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is excreted as unchanged drug, 3,4-methylenedioxyamphetamine (MDA), and free and glucuronidated/sulfated 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) metabolites. The aim of this paper is to describe the pattern and timeframe ...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/33.8.439
更新日期:2009-10-01 00:00:00
abstract::A rapid and efficient high-performance liquid chromatographic method using a reversed-phase eluent of methanol-water with butylamine on a silica column was developed for the separation and quantitation of clomipramine (CMI), its demethylated metabolites (desmethyl-clomipramine and didesmethyl-clomipramine [DDCMI]), an...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/20.2.101
更新日期:1996-03-01 00:00:00
abstract::Improvements have been made in recent years in on-site or point-of-care (POC) immunoassay testing devices. We evaluated the DrugCheck 9 cup, a new qualitative visually read, competitive binding, immunoassay cup that measures nine analytes. The study was performed according to the recent National Laboratory Certificati...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/28.3.190
更新日期:2004-04-01 00:00:00
abstract::This study shows a simple, rapid, and specific method for the quantitative determination of cyanide ion in body fluids, especially blood, by fluorimetry. It is based upon the transformation of cyanide ion into hydrocyanic acid, which then reacts with 2,3-naphthalenedialdehyde and taurine in a self-contained system. Th...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/22.5.363
更新日期:1998-09-01 00:00:00
abstract::Exemplars of current commercial breath-alcohol simulators were studied to ascertain their suitability for control tests and as calibrators in breath-alcohol analysis. Temperature, effluent volumes and pressures, effluent-alcohol concentration, and alcohol depletion were measured for simulators coupled with various cur...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/15.5.272
更新日期:1991-09-01 00:00:00
abstract::The relationship between blood cocaine concentrations and pharmacological effects is of both theoretical and practical interest. This study utilized a computer-assisted smoking device for the delivery of three active doses (10, 20, and 40 mg) of cocaine base to seven human volunteers. Doses were administered in an asc...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/26.7.382
更新日期:2002-10-01 00:00:00
abstract::The aim of this study is to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid and both EtG and ethyl sulfate (EtS) in blood and urine following intense use of mouthwash and ingestion of nonalcoholic wine, which are proven to contain 3 mg/L EtG, 1.5 mg/L EtS, and 0.2 g/L ethanol. Twelve subjects p...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/34.2.84
更新日期:2010-03-01 00:00:00
abstract::Bleach, nitrite, chromate, and hydrogen peroxide-peroxidase are effective urine adulterants used by the illicit drug users to conceal marijuana-positive results. Methods for detecting nitrite and chromate are available. Effects of other oxidizing agents that could possibly be used as adulterants and are difficult to d...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/26.7.460
更新日期:2002-10-01 00:00:00
abstract::Publications reporting concentrations of caffeine in postmortem blood were reviewed if the cause of death was attributed to overdosing (poisoning) with drugs. Age and gender of the deceased, the manner of death (accident, suicide or undetermined) and types of co-ingested drugs were evaluated in relation to the concent...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章,评审
doi:10.1093/jat/bkx011
更新日期:2017-04-01 00:00:00
abstract::Methods for extraction of cocaine, some of its metabolites, morphine, and codeine from hair and methods for analyzing the extracts have been investigated. Results of these studies have shown that extractions with 0.1N HCl are efficient at removing the target compounds from hair and appear to be as effective as enzymat...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/17.7.389
更新日期:1993-11-01 00:00:00
abstract::An isotope dilution gas chromatography-tandem mass spectrometric (GC-MS-MS) method was developed for quantitating the urinary metabolites of the organophosphorus nerve agents sarin, soman, tabun (GA), VX, and GF. Urine samples were concentrated by codistillation with acetonitrile, derivatized by methylation with diazo...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/26.1.6
更新日期:2002-01-01 00:00:00
abstract::Urine drug testing is common for workplace drug testing, prescription management, emergency medicine and the criminal justice system. Unsurprisingly, with the significant consequences based upon the results of urine drug testing, a donor in need of concealing the contents of their sample is highly motivated to cheat t...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/bkw119
更新日期:2017-03-01 00:00:00
abstract::In recent years, several synthetic cannabinoid compounds have become popular recreational drugs of abuse because of their psychoactive properties. This paper presents toxicological findings of synthetic cannabinoids in whole blood from some cases of severe intoxication including quantitative data from recreational use...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/bkt068
更新日期:2013-10-01 00:00:00
abstract::A method that measures 12 analytes in urine and reflects possible exposure to pesticides was developed. The sample preparation involves enzyme hydrolysis and solvent extraction through the use of laboratory robotics, followed by phase-transfer catalysis derivatization and silica cleanup. Samples are analyzed by capill...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/19.5.323
更新日期:1995-09-01 00:00:00
abstract::A rapid, simple, highly sensitive procedure for the simultaneous analysis of bromazepam, alprazolam, clonazepam, lorazepam, oxazepam, diazepam, midazolam, flurazepam, flunitrazepam, nordiazepam, triazolam, temazepam, nitrazepam, and chlordiazepoxide in oral fluid is described, using liquid chromatography coupled to a ...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/31.9.596
更新日期:2007-11-01 00:00:00
abstract::In June 1986, an epidemic of poisoning occurred in Sierra Leone, West Africa; it involved 49 persons--with 14 deaths. Our laboratory's approach and investigation of this incident is described. Using positive chemical ionization mass spectrometry and nuclear magnetic resonance spectroscopy, the toxicant was identified ...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/14.4.213
更新日期:1990-07-01 00:00:00
abstract::Data from previous experimental studies on the detection time of oxazepam and zopiclone in biological matrices are limited. The aim of this study was to examine the detection time in urine and oral fluid after single oral doses of oxazepam and zopiclone. Ten healthy volunteers received 25 mg of oxazepam in the evening...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/bky083
更新日期:2019-06-01 00:00:00
abstract::The Connecticut Department of Public Safety laboratory recently addressed a legal challenge to a hospital alcohol dehydrogenase (ADH)-based serum ethanol determination based on the suggestion of interference by lactate dehydrogenase (LDH)-catalyzed oxidation of lactate. Both ADH- and LDH-oxidations require NAD(+) (pre...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/33.8.561
更新日期:2009-10-01 00:00:00
abstract::A sensitive and specific method was developed for the quantitative analysis of l-alpha-acetylmethadol (LAAM), l-alpha-acetyl-N-normethadol (norLAAM), and l-alpha-acetyl-N,N-dinormethadol (dinorLAAM) in hair. In the development of this method, it was determined that sample pretreatment methods performed by the laborato...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/21.6.420
更新日期:1997-10-01 00:00:00
abstract::A new method was developed to apply the advantages of automated gas chromatographic headspace analysis to delayed measurement of alcohol in whole breath (W-B). End-expiratory breath and vapor-alcohol samples were collected in sealed, heated 22-mL glass vials, stored for 0-15 days, and thereafter analyzed for alcohol b...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/6.5.217
更新日期:1982-09-01 00:00:00
abstract::Solid-phase extraction (SPE) and a one-step derivatization are combined with gas chromatography-negative ion chemical ionization-mass spectrometry to simplify a previously reported method for the determination of naltrexone and its metabolite, 6-beta-naltrexol, in human plasma. Deuterated isotopomers of naltrexone and...
journal_title:Journal of analytical toxicology
pub_type: 临床试验,杂志文章
doi:10.1093/jat/21.4.252
更新日期:1997-07-01 00:00:00
abstract::This report describes a gas chromatographic procedure using a packed column and a flame ionization detector, which is suitable for the therapeutic monitoring of N-methylformamide (N-MF). N-MF is a polar compound that induces cancer cell maturation in vitro and exhibits antitumor activity with human tumors xenografted ...
journal_title:Journal of analytical toxicology
pub_type: 杂志文章
doi:10.1093/jat/7.2.89
更新日期:1983-03-01 00:00:00