Abstract:
:Designer drugs of the methylenedioxyphenylalkylamine type are increasingly abused. Studies on their metabolism in humans are necessary to develop a reliable gas chromatography--mass spectrometry (GC-MS) screening procedure. Such a method must allow their detection in urine for drug testing in clinical and forensic toxicology. Studies on racemic methylenedioxyamphetamine (MDA), methylenedioxymetamphetamine (MDMA), methylenedioxyethylamphetamine (MDE), benzodioxazolylbutanamine (BDB), and N-methylbenzodioxazolylbutanamine (MBDB) are presented. The metabolites were identified by GC-MS after enzymatic hydrolysis, isolation (pH 4.5 and 8-9), and derivatization (acetylation followed by methylation). The drugs undergo two overlapping metabolic pathways: O-dealkylation of the methylenedioxy group to dihydroxy derivatives followed by methylation of one of the hydroxy groups and successive degradation of the side chain to N-dealkyl and deaminooxo metabolites. MDA, MDMA, and MDE are subsequently metabolized to glycine conjugates of the corresponding 3,4-disubstituted benzoic acids. The hydroxy metabolites are excreted in a conjugated form. Based on these results, a GC-MS procedure was developed for simultaneous screening and identification of these designer drugs and/or their metabolites in urine after acid hydrolysis, isolation at pH 8-9, and acetylation. With use of mass chromatography with the most characteristic fragment ions m/z 58, 72, 86, 150, 162, 164, 176, and 178, the presence of the designer drugs was indicated and the peak underlying spectra could be identified by computerized comparison with reference spectra recorded during the presented studies. The procedure was suitable to detect an abuse of or an intoxication with the studied designer drugs (detection limit 5-50 ng/ml).
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Maurer HHdoi
10.1097/00007691-199608000-00027subject
Has Abstractpub_date
1996-08-01 00:00:00pages
465-70issue
4eissn
0163-4356issn
1536-3694journal_volume
18pub_type
杂志文章abstract::The monitoring of plasma olanzapine concentrations has been found to be an important and useful tool for optimizing psychiatric treatment. The present study investigated the effect that clinical factors, such as smoking and age, and functional polymorphisms of UGT1A4, CYP1A2, and CYP2D6 genes have on plasma olanzapine...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31816336fd
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:No information on the pharmacokinetic characteristics of amlodipine (AML) metabolites is available. This study aimed to develop a method based on isocratic liquid chromatography coupled to tandem mass spectrometry for the simultaneous determination of AML and its 2 major metabolites, dehydroamlodipine (DH-AM...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000449
更新日期:2017-12-01 00:00:00
abstract::Several studies have reported that the cytochrome P450 (CYP) 2D6 plays an important role in the fluvoxamine metabolism. However, some other studies have reported that the CYP2D6 genotype has no major impact on the fluvoxamine concentration. This study investigated the dose-dependent effect of CYP2D6-variant alleles on...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31818d73b3
更新日期:2008-12-01 00:00:00
abstract::An index of desipramine (DMI) hydroxylation, calculated as the ratio between the amounts of DMI and 2-hydroxydesipramine (2-OH-DMI) excreted in urine after 25 mg orally, was determined in 16 depressed patients. The index varied almost 100-fold between the patients and correlated significantly to the steady-state plasm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198706000-00001
更新日期:1987-06-01 00:00:00
abstract::Determination of plasma methadone is essential in connection with dose adjustments for patients participating in methadone maintenance programs. We successfully adapted the existing fluorescence polarization immunoassay (FPIA) kit intended for urinary methadone to plasma assays. A concentration interval of 50-900 ng/m...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::The performance of the ROCHE FP NAPA reagent, a newly reformulated monoclonal antibody-based fluorescence polarization immunoassay (FPIA) for N-acetylprocainamide, was compared with two commercially available polyclonal antibody-based immunoassays, the Abbott TDx and Syva EMIT. Although excellent correlation was obser...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199406000-00013
更新日期:1994-06-01 00:00:00
abstract::Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often diff...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199806000-00003
更新日期:1998-06-01 00:00:00
abstract::In a phase I-II study, the authors evaluated the intracellular pharmacokinetics, toxicity, and efficiency of a high dose of mitoxantrone given as first induction in acute non-lymphocytic leukemia. Twenty-two patients with previously untreated de novo ANLL were included and received 30 or 40 mg/m2 mitoxantrone on day 1...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199812000-00010
更新日期:1998-12-01 00:00:00
abstract::Sotrastaurin (AEB071) is an investigational immunosuppressant that blocks T-lymphocyte activation through protein kinase C inhibition. It is currently in Phase II of clinical development for the prevention of acute rejection after solid organ transplantation. In renal transplant clinical trials, sotrastaurin has been ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e3181ee9e26
更新日期:2010-10-01 00:00:00
abstract::The authors refer to their experience with alternative matrices to supervise the methadone therapy of heroin abusers. For this purpose, hair, sweat, and urine samples were collected from 10 heroin addicts and from a control group and were submitted to gas chromatographic/mass spectroscopic analysis for methadone and i...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31811f1bbe
更新日期:2007-08-01 00:00:00
abstract::Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the active moiety of MMF, im...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181a23f1a
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Analysis of residual gene expression of the nuclear factor of activated T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to monitor therapy with calcineurin inhibitors. The availability of commercial primer sets (Search-LC) and the well-established assay protocol makes this bio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000340
更新日期:2016-12-01 00:00:00
abstract::Hydroxylation of midazolam (MDZ) is mediated almost exclusively by CYP3A isoforms. The authors describe a high-performance liquid chromatography assay involving MDZ, 1'-hydroxymidazolam, and 4-hydroxymidazolam in plasma. The compounds were eluted on an Ultrasphere ODS, 3-microm particle size, 7.5 cm x 4.6 mm reversed-...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199806000-00013
更新日期:1998-06-01 00:00:00
abstract::A highly sensitive, specific method for determining chloramphenicol levels in human blood plasma and cerebrospinal fluid is described. The method uses high performance liquid chromatography for the analysis, requires minimal quantities of patient specimen, and thus is suitable for use in newborn and pediatric patients...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198709000-00016
更新日期:1987-09-01 00:00:00
abstract::Drugs metabolized by cytochrome CYP3A isoenzymes have wide interindividual variability and normally distributed plasma clearance distributions. This makes precise dosing difficult to achieve clinically, which may compromise safe therapy. We hypothesized that with potent inhibition of CYP3A, we could clinically render ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000194497.55269.d9
更新日期:2006-04-01 00:00:00
abstract::Rapamycin (RAPA) is a new immunosuppressive drug with a potency similar to that of FK506 and up to a 100-fold greater than that of cyclosporine (CsA). RAPA has shown to be efficacious in the prolongation of allograft survival in a number of animal models. In early studies, RAPA was administered on a dose/weight basis,...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199312000-00004
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:Despite significant interindividual variability in prednisolone pharmacokinetics and potentially serious consequences with inadequate or excessive exposure, monitoring of prednisolone levels is not employed to guide therapy. As ultrahigh-performance liquid chromatography-tandem mass spectrometry methods can ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31829daae4
更新日期:2014-02-01 00:00:00
abstract::An analytical technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI--MS) has been developed for the simultaneous determination of five protease inhibitors (PIs): saquinavir, indinavir, ritonavir, nelfinavir, and amprenavir; and three non-nucleoside reverse transcriptase inhibitors...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200108000-00010
更新日期:2001-08-01 00:00:00
abstract::A simple and rapid reversed-phase C-18 high-performance liquid chromatography (HPLC) assay without a prior extraction step for dihydroquinidine (HQD) in serum is described. The method is selective and useful for monitoring HQD and its presumed metabolites, quinidine (QD), N-oxide QD, 3-hydroxy QD (3-OHQD), and 10-11-d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198412000-00017
更新日期:1984-01-01 00:00:00
abstract::The binding characteristics of the antiepileptic agent and teratogen valproic acid for human serum and human placenta were investigated utilizing equilibrium dialysis of the drugs in serum and in homogenates of whole placenta so that the transplacental transfer of the drug could be better defined. A low-capacity, high...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000158077.07836.9a
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:In psychopharmacology, treatment with psychotropic drugs is often suboptimal, mainly because of the high interindividual variability in pharmacokinetic properties. Therapeutic drug monitoring (TDM) can be a valuable tool for monitoring the individual effects of a prescribed dosage in a patient, and it facili...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000197
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited, therefore application of minimally invasive drug sampling techniques, such as dried blood spo...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000670
更新日期:2019-12-01 00:00:00
abstract::Simplified pharmacokinetic methods have been used to estimate caffeine clearance in subjects with liver disease. There is a need to have a reliable, easy to implement method for research and possible clinical use. This study evaluates the use of Bayesian pharmacokinetic forecasting techniques to estimate caffeine clea...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199802000-00015
更新日期:1998-02-01 00:00:00
abstract::A 64-year-old man with chronic renal insufficiency was hospitalized with dysphagia and inability to keep his head erect 11 months after beginning procainamide hydrochloride (PA) for control of atrial flutter. Evaluation revealed esophageal dysmotility, worsening renal function, and elevated serum PA and N-acetylprocai...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199306000-00013
更新日期:1993-06-01 00:00:00
abstract::The immunosuppressant mycophenolic acid (MPA) used for solid organ transplantation is predominantly metabolized to a pharmacologically inactive phenolic glucuronide (MPAG) and, to a lesser extent, to the pharmacologically active acyl glucuronide (AcMPAG). The recently introduced CEDIA Mycophenolic Acid Assay from Micr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181cc342a
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:In this study, the authors studied the effect of thioridazine (TDZ) on the pharmacokinetic profile of quetiapine (QTP) in Taiwanese patients with schizophrenia. METHODS:Sixteen subjects with schizophrenia were recruited for this study. The authors pretreated 8 patients with TDZ 50 mg daily continuously give...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究
doi:10.1097/FTD.0b013e31825479cc
更新日期:2012-06-01 00:00:00
abstract::Using mobile long-term electroencephalographic (EEG) monitoring in 7 absence epilepsy patients, the course of spike-wave discharge rate before and during valproate monotherapy was measured and compared to the profile of valproic acid serum level. Correlation analysis was done, taking into account an eventual time dela...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198406000-00008
更新日期:1984-01-01 00:00:00
abstract::The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or th...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198911000-00013
更新日期:1989-11-01 00:00:00
abstract::The ring sulfoxidation of thioridazine (THD), a widely used neuroleptic agent, yields two diastereoisomeric pairs, fast- and slow-eluting (FE and SE) thioridazine 5-sulfoxide (THD 5-SO). Until now, studies in which concentrations of these metabolites were measured in THD-treated patients have revealed no significant d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1991-07-01 00:00:00
abstract::Gabapentin is used in analgesic treatment of neuropathic pain, and large interindividual variation has been observed in the pharmacokinetics (PK) of the drug. The aim of this study was to develop a population PK model for gabapentin appropriate for monitoring patients with neuropathic pain and for individualizing thei...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e318194767d
更新日期:2009-02-01 00:00:00