Abstract:
INTRODUCTION:Gabapentin (Neurontin) and levetiracetam (Keppra) are anticonvulsants with novel structures and suggested therapeutic ranges of 2-10 mg/L and 6-20 mg/L, respectively. Gabapentin is also used extensively to manage neuropathic pain, and for this indication, wherein higher doses are prescribed, plasma concentrations of 15-30 mg/L are typical. OBJECTIVE:Here, we describe a simple rapid assay to support therapeutic drug monitoring of gabapentin and levetiracetam in plasma by ultra-pressure liquid chromatography couples to tandem mass spectrometry (UPLC-MS/MS) detection. METHODS:After the addition of internal standard and protein precipitation of patient plasma with methanol:acetonitrile in a 50:50 ratio, 1 μL of supernatant sample is injected onto an Acquity UPLC HSS T3, 1.8 μm, 2.1 × 50 mm (Waters) column. Elution occurs using a linear gradient of acetonitrile and water, each having 0.1% formic acid added. The column is eluted into a Waters Acquity UPLC TQD, operating in a positive mode to detect gabapentin at transition 172.18 > 154.11, levetiracetam at 171.11 > 126, and internal standard (3-amino-2-naphthoic acid) at 188.06 > 170. Secondary transitions for each analyte are also monitored for gabapentin at 172.18 > 137.06, levetiracetam at 171.11 > 154, and internal standard at 188.06 > 115. Runtime is 1.5 minutes per injection with baseline resolved chromatographic separation. RESULTS:The analytical measurement ranges were 1-150 mg/L for gabapentin and for levetiracetam. Intra-assay imprecision by the coefficient of variance (CV) was less than 8% and interassay CV was less than 5% for both analytes, at 4 different concentrations. Results obtained from patient samples were compared with results generated by established high-performance liquid chromatography-UV methods with the following regression statistics: y = 1.12x - 0.77, r = 0.996, Sy, x = 0.89, and n = 29 for gabapentin and y = 0.991x + 0.70, r = 0.997, Sy, x = 2.24, and n = 30 for levetiracetam. No analytical interferences were identified. CONCLUSION:: In summary, a simple reliable UPLC-MS/MS method was developed and validated for routine clinical monitoring of gabapentin and levetiracetam.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Juenke JM,Brown PI,Johnson-Davis KL,McMillin GAdoi
10.1097/FTD.0b013e31820b1fcesubject
Has Abstractpub_date
2011-04-01 00:00:00pages
209-13issue
2eissn
0163-4356issn
1536-3694journal_volume
33pub_type
杂志文章abstract::Trough levels (TL) of cyclosporine (CS) measured in serum by the polyclonal radioimmunoassay (SR) are useful for dissecting the etiology of clinical events, but they are a poor guide to dosage adjustments. In renal transplant patients immunosuppressed by low doses of prednisone and CS given orally, once-a-day TL (24-h...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::In a prospective study over 6 months, the relationship between serum lipid parameters and CsA whole blood trough concentrations was investigated in 39 renal transplant recipients receiving a triple immunosuppressive therapy with cyclosporin (CsA), azathioprine and prednisone. CsA trough concentrations were measured wi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199704000-00004
更新日期:1997-04-01 00:00:00
abstract::We describe a patient with invasive pulmonary aspergillosis on extracorporeal membrane oxygenation therapy in which therapeutic drug monitoring and individualization of therapy by measuring voriconazole plasma concentrations were performed. ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181898b0c
更新日期:2008-12-01 00:00:00
abstract::One tablet containing 755 mg of lithium tryptophanate (10.8 mEq of lithium) was administered to eight healthy volunteers. The main pharmacokinetic parameters for the group of subjects were estimated. Pharmacokinetic parameters (mean +/- SD) from plasma and saliva were respectively: half life (t1/2) 17 +/- 6 vs. 21.8 +...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198803000-00004
更新日期:1988-01-01 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
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::A sensitive method for monitoring serum piroxicam (Feldene) is described. The assay requires 1.0 ml of specimen and involves chloroform extraction from an acidified mixture followed by concentration and injection into a liquid chromatograph. Column effluent is monitored at 330 nm. Retention times of piroxicam and the ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198306000-00017
更新日期:1983-06-01 00:00:00
abstract::Drug discovery programs are actively exploring for therapeutic agents targeting enzymes and receptors regulating sphingolipid metabolism and biologic functions. FTY720 is a close structural analogue of sphingosine with immunomodulatory properties. After oral administration, FTY720 is phosphorylated by sphingosine kina...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200412000-00001
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Posaconazole is an azole antifungal agent with a broad spectrum of activity and a manageable side-effect profile. Although the pharmacokinetics of posaconazole have been described in healthy volunteers who received the drug by means of a nasogastric tube or with nutritional supplements, the pharmacokinetics ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e31821fb197
更新日期:2011-08-01 00:00:00
abstract::Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured....
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199001000-00008
更新日期:1990-01-01 00:00:00
abstract::Since the late 90s, biopharmaceuticals targeting tumor necrosis factor alpha have revolutionized the treatment of moderately to severely active inflammatory bowel disease. The robust efficacy witnessed in many patients stands in stark contrast with the observation of a proportion of patients who fail to respond or who...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0000000000000394
更新日期:2017-08-01 00:00:00
abstract::The major goal of immunosuppressive development is improved selectivity of the drug's inhibitory action against T and B cell-mediated as opposed to nonspecific granulocyte-, monocyte-, and macrophage-mediated resistance. This enterprise demands increased knowledge of alloantigen-induced stimulation, signal transductio...
journal_title:Therapeutic drug monitoring
pub_type: 历史文章,杂志文章
doi:10.1097/00007691-199512000-00002
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:Because of its superior sensitivity and specificity, multianalyte high-performance liquid chromatography coupled with tandem mass spectrometry has become the gold standard in clinical toxicology. Although several qualitative and quantitative liquid chromatography coupled with tandem mass spectrometry assays ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000429
更新日期:2017-10-01 00:00:00
abstract::The authors report preliminary findings on the potential contribution of CYP2C19 isoenzyme to the human metabolism of N-desmethylclobazam (N-CLB), the main active metabolite of clobazam (CLB), a benzodiazepine frequently used as add-on therapy in patients with refractory epilepsy. Two children on CLB treatment showing...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200212000-00009
更新日期:2002-12-01 00:00:00
abstract::Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to be a useful biomarker of early diabetic nephropathy. We studied whether L-PGDS is also a marker of gentamicin (GM)-induced renal damage in the "creatinine-blind" range. A prospective study was conducted in 6 patients who were g...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31819566f1
更新日期:2009-02-01 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::A computer-based approach for estimating pharmacokinetic data and predicting plasma drug concentrations based on two measurements of plasma drug concentrations was compared with a standard two-point method for estimating aminoglycoside (AG) pharmacokinetic parameters. The computer-based technique was also used to pred...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198507030-00003
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:There is a high coincidence between obesity and psychiatric disorders including depression. Depressive disorders are commonly treated with antidepressants, including the selective serotonin reuptake inhibitor Lexapro (escitalopram). Although candidates for elective Roux-en-Y gastric bypass (RYGB) surgery may...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000146
更新日期:2015-06-01 00:00:00
abstract::This study develops a population pharmacokinetic model for lamotrigine (LTG) in Spanish and German patients diagnosed with epilepsy. LTG steady-state plasma concentration data from therapeutic drug monitoring were collected retrospectively from 600 patients, with a total of 1699 plasma drug concentrations. The data we...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31817fd4d4
更新日期:2008-08-01 00:00:00
abstract::A rapid and sensitive method for the quantitation of valproic acid in tears has been developed using gas chromatography/electron capture negative chemical ionization/mass spectrometry. Valproic acid was converted directly into its pentafluorobenzyl ester derivative without the need to perform any extraction from the b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200012000-00011
更新日期:2000-12-01 00:00:00
abstract::Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198706000-00014
更新日期:1987-06-01 00:00:00
abstract::Whole blood steady-state trough concentrations of cyclosporine were measured by radioimmunoassay (RIA) and TDx assays employing monoclonal antibodies in 82 samples from 39 renal transplant patients. Intra- and interassay coefficients of variation for the new TDx technique averaged 3.2 and 5.4%, respectively. In the co...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199109000-00012
更新日期:1991-09-01 00:00:00
abstract::Therapeutic drug monitoring in antituberculosis chemotherapy may play a strategic role in improving outcomes in selected patients. The most important use is in assisting clinicians to optimize therapy to achieve success and minimize toxicity. The other principal indication lies in the management of interaction of anti...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199810000-00004
更新日期:1998-10-01 00:00:00
abstract:INTRODUCTION:Proton pump inhibitors (PPIs) are often prescribed posttransplantation to prevent gastrointestinal complications. A series of recent studies have reported a relationship between PPI comedication and decreased mycophenolic acid (MPA) exposure. The objective of this subanalysis of the CLEAR data set was to d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FTD.0b013e318206a1b1
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Non-vitamin K antagonist oral anticoagulants (NOACs) are approved for several indications for prophylaxis of thromboembolism at fixed oral doses. The analysis of NOAC activity/concentration may be required in special patient populations. Heptest coagulation assay determines both factor Xa and thrombin inhibi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000157
更新日期:2015-06-01 00:00:00
abstract::The purpose of this study was to construct a population pharmacokinetic (PK) metabolism (MB) model to describe ciprofloxacin (C) concentrations in plasma and vitreous and aqueous humors in 26 patients. Ciprofloxacin was given as a 3-day oral prophylactic treatment to 26 patients before vitrectomy. Plasma, vitreous, an...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200408000-00010
更新日期:2004-08-01 00:00:00
abstract::This laboratory has developed a simple and efficient solid-phase extraction method that is combined with a high-performance liquid chromatographic method for rapid and precise therapeutic monitoring of haloperidol (Haldol) blood levels. The solid-phase extraction utilizes a mixed bed column. Sensitivity of the chromat...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199410000-00011
更新日期:1994-10-01 00:00:00
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::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:OBJECTIVE:The aim of the study is to characterize the pharmacokinetics and the gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC-MPS) in de novo kidney transplant patients of Hispanic ethnicity. MATERIALS AND METHODS:The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31820271c3
更新日期:2011-02-01 00:00:00