Abstract:
:A novel liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for quantification of topiramate (TPM) and its metabolites 10-hydroxy topiramate (10-OH-TPM), 9-hydroxy topiramate (9-OH-TPM), and 4,5-O-desisopropylidene topiramate (4,5-diol-TPM) in plasma and urine. The method uses 0.5 mL of plasma or 1 mL of urine that is extracted with diethyl ether and analyzed by LC-MS. Positive ion mode detection enables tandem mass spectrometric (MS/MS) identification of the aforementioned four compounds. Calibration curves of TPM, 4,5-diol-TPM, 9-OH-TPM, and 10-OH-TPM in plasma and urine were prepared and validated over the concentration range of 0.625 to 40 microg/mL using TPM-d(12) as an internal standard. Calibration curves were linear over this concentration range for TPM and its metabolites. Accuracy and precision ranged in urine from 83% to 114% and 4% to 13% (%CV), respectively, and in plasma from 82% to 108% and 6% to 13%, respectively. The applicability of the assay was evaluated by analyzing plasma samples from a healthy subject who received a single oral dose of TPM (200 mg) and urine samples from 11 patients with epilepsy treated with TPM (daily dose between 100 to 600 mg) alone or with other antiepileptic drugs. Only TPM was detected and quantified in the plasma samples, and its concentration ranged between 0.7 and 4.3 microg/mL. The concentrations of TPM and 10-OH TPM were quantifiable in all urine samples and ranged from 20 to 300 microg/mL for TPM and from 1 to 50 microg/mL for 10-OH-TPM. The metabolites 4,5-diol-TPM and 9-OH-TPM were also detected in all urine samples, but their concentrations were quantifiable only in 4 patients. An unidentified peak in the chromatograms obtained from patients' urine was attributed to 2,3-O-desisopropylidene topiramate (2,3-diol-TPM). Due to a lack of reference material of 2,3-diol TPM and the similar MS/MS spectrum with 4,5-diol-TPM, the calibration curves of 4,5-diol-TPM were used for the quantification of its isomer 2,3-diol-TPM. Based on these determinations, the apparent 2,3-diol-TPM-to-TPM concentration ratio in patients' urine ranged from 0.05 to 0.51 and the 10-OH-TPM-to-TPM ratio ranged from 0.02 to 0.17. In conclusion, a novel LC-MS method for the assay of TPM and four of its metabolites in plasma and urine was developed. Its utilization for analysis of urine samples from patients with epilepsy showed that the method was suitable for analysis of TPM and its metabolites in clinical samples. Two quantitatively significant TPM metabolites (10-OH-TPM and 2,3-diol-TPM) and two quantitatively minor metabolites (9-OH-TPM and 4,5-diol-TPM) were detected and quantified in urine samples from patients with epilepsy.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Britzi M,Soback S,Isoherranen N,Levy RH,Perucca E,Doose DR,Maryanoff BE,Bialer Mdoi
10.1097/00007691-200306000-00012subject
Has Abstractpub_date
2003-06-01 00:00:00pages
314-22issue
3eissn
0163-4356issn
1536-3694journal_volume
25pub_type
杂志文章abstract:BACKGROUND:Sirolimus is a mammalian target of rapamycin inhibitor that is being used to prevent organ rejection in kidney transplant patients often in combination with calcineurin inhibitors (CNIs; cyclosporine and tacrolimus). All 3 drugs are metabolized primarily by CYP3As. Clinical drug-drug interaction (DDI) studie...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000314
更新日期:2016-10-01 00:00:00
abstract::The authors report the use of high-performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) for the quantification of indomethacin (IND) in plasma with microscale sample preparation. Plasma samples (100 microL) and mefanamic acid (internal standard [IS]), buffered to pH 3.5, were prepar...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199812000-00020
更新日期:1998-12-01 00:00:00
abstract::Recently, a semiautomated fluorescence polarization immunoassay (FPIA) for determination of parent cyclosporin (CsA) has been developed for the Abbott AxSYM system. The new CsA assay measures the drug from an extracted whole blood specimen. The authors report here the evaluation of this new assay and the comparison wi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200008000-00018
更新日期:2000-08-01 00:00:00
abstract::The effect of plasma exchange (PE) on the pharmacokinetics of flumequine (Apurone) was studied in eight patients receiving a single oral dose of 800 mg. The maximum concentration (38 micrograms/ml) and time to maximum concentration (2.6 h) values were not significantly altered by PE beginning 3 h after administration ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199107000-00003
更新日期:1991-07-01 00:00:00
abstract:OBJECTIVES:The objective of the present study was to perform an external evaluation of published linezolid population pharmacokinetic and pharmacodynamic models, in order to evaluate the predictive performance using an independent dataset. Another aim was to offer an elegant environment for display and simulation of bo...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000816
更新日期:2020-09-28 00:00:00
abstract::Mixed-effect modeling has been suggested as a possible tool to detect and describe drug interactions in patient populations receiving drug combinations for the treatment of disease states. The mixed-effect modeling program, NONMEM, was used to measure the effects of the well-known digoxin-quinidine and digoxin-verapam...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199602000-00008
更新日期:1996-02-01 00:00:00
abstract::The clinical correlates of methylphenidate blood levels in hyper-active children and normal adults were examined in five studies. Although occasional correlations between blood levels and neuroendocrine response were noted within subjects along the pharmacokinetic time profile of the drug, no significant associations ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198412000-00001
更新日期:1984-01-01 00:00:00
abstract::A sensitive and specific direct-injection high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass-spectrometry (HPLC-APCI-MS-MS) method has been developed for the rapid identification and quantitation of seven tricyclic antidepressants-amitriptyline, nortriptyline, doxepin, dosulepi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200208000-00013
更新日期:2002-08-01 00:00:00
abstract::The immunosuppressive potential of mycophenolic acid (MPA) correlates well with MPA exposure [area under the concentration-time curve (AUC)]. Monitoring MPA AUC is important and helpful for maintaining the efficacy of mycophenolate mofetil while minimizing its side effects, but full MPA AUC monitoring is laborious, co...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181559f8a
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND:A fast and easy-to-use liquid chromatography-tandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000438
更新日期:2017-10-01 00:00:00
abstract::The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198303000-00004
更新日期:1983-01-01 00:00:00
abstract::We describe the case of a pediatric patient on azathioprine therapy with previously undiagnosed homozygote thiopurine S-methyltransferase (TPMT) deficiency, resulting in myelotoxic thiopurine metabolite levels. The patient was successfully treated with a very low azathioprine dose of 50 mg once a week (4% of standard ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000366
更新日期:2017-02-01 00:00:00
abstract::Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrom...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200106000-00008
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND:The efficacy of drugs for the treatment of substance-related disorders is moderate at best. Therapeutic drug monitoring (TDM) could be an instrument to improve outcomes. Because TDM for most of those drugs is not established, the authors reviewed the literature and built a rating scale to detect the potentia...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e31822fbf7c
更新日期:2011-10-01 00:00:00
abstract::Calculated creatinine clearance (CrCL) estimates are frequently used as estimates of aminoglycoside clearance (AGCL), despite being inadequately studied. Thirty surgical intensive care unit (SICU) patients with stable serum creatinines (0.6-6.3 mg/dl) and steady-state aminoglycoside levels were studied. A one-compartm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198903000-00006
更新日期:1989-01-01 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::A study was conducted to determine whether assay-specific quantitative differences exist in the determination of vancomycin serum concentrations obtained from patients with renal dysfunction. Vancomycin serum concentrations were obtained during the first week of therapy for each of three time intervals: 48-96 h, 96-14...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199612000-00004
更新日期:1996-12-01 00:00:00
abstract::Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred f...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200102000-00007
更新日期:2001-02-01 00:00:00
abstract::A population pharmacokinetic model was developed after administration of orogastric and/or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants. Plasma indomethacin concentrations (n=227) were obtained from 90 preterm infants of median gestational age 27 weeks, mean postnatal age o...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0b013e31815b3e13
更新日期:2007-12-01 00:00:00
abstract::OKT3 is a murine monoclonal antibody of the immunoglobulin IgG2a isotype. The target of OKT3, CD3, is a 17-20 kilodalton (kD) molecule that is part of a multimolecular complex found only on mature T cells and medullary thymocytes. This complex is uniquely situated next to the T-cell receptor for antigen. An interactio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199512000-00012
更新日期:1995-12-01 00:00:00
abstract::Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary p...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199708000-00007
更新日期:1997-08-01 00:00:00
abstract::The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198309000-00014
更新日期:1983-01-01 00:00:00
abstract::Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and ne...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000710
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmac...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0000000000000572
更新日期:2019-02-01 00:00:00
abstract::Six groups of six male Wistar rats were administered methadone in their drinking water over the concentration range 0-0.25 mg/ml. Hair and trunk blood samples were collected after a 6-week period of drug administration. Immunoreactive methadone was measured by radioimmunoassay and methadone and its major metabolite, 2...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199612000-00014
更新日期:1996-12-01 00:00:00
abstract::The authors aimed to evaluate the utility of the history and clinical signs for predicting ingestion of poisons in children. A prospective cohort study was performed of all patients presenting with suspected poisoning to a pediatric emergency department over a 13-month period. Clinical data were collected on a preform...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200312000-00012
更新日期:2003-12-01 00:00:00
abstract::With the introduction of a cyclosporin monitoring strategy based on the use of a sample collected 2 hours after dosing (C2) rather than the predose sample (C0), there was concern that the differences in blood cyclosporin results from the various assay systems would result in assay-specific target ranges for C2 monitor...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00007691-200304000-00005
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis versus illegal and medical cannabis use were also investigated. METHODS:Sera ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000683
更新日期:2020-02-01 00:00:00
abstract::Differences in product formulations have been shown to affect the therapeutic response by altering the relative bioavailability and pharmacokinetics of a drug. The relative bioavailability and pharmacokinetics of carbamazepine tablets (CBZ) and a chewable tablet formulation were evaluated in 10 normal healthy subjects...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-198703000-00006
更新日期:1987-01-01 00:00:00
abstract::The postulated therapeutic activity of nortriptyline metabolites has prompted investigation of dosage adjustments based on plasma levels of nortriptyline (NT) and its metabolites. The method assumes that metabolite concentrations vary independently of nortriptyline concentrations among patients. This study tests that ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198905000-00001
更新日期:1989-01-01 00:00:00