Streit, Frank

[["dc.bibliographiccitation.firstpage","1170"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Neurology Neurosurgery & Psychiatry"],["dc.bibliographiccitation.lastpage","1173"],["dc.bibliographiccitation.volume","83"],["dc.contributor.author","Decard, Bernhard F."],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Grunwald, Thomas"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Stroet, Anke"],["dc.contributor.author","Niggemeier, Petra"],["dc.contributor.author","Schottstedt, Volkmar"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Chan, Andrew"],["dc.date.accessioned","2018-11-07T09:02:57Z"],["dc.date.available","2018-11-07T09:02:57Z"],["dc.date.issued","2012"],["dc.description.abstract","Objective Vitamin D deficiency and Epstein-Barr virus (EBV) infection may be associated with the development of multiple sclerosis (MS). We investigated serum 25-hydroxyvitamin D (25-OH-D) levels and anti-EBV immunoreactivity in 25 individuals before the first clinical manifestation of MS. Patients and methods 56 serum samples of 25 individuals who had donated blood prior to the first clinical MS manifestation (clinically isolated syndrome (CIS)) (four male subjects, 21 female subjects, mean age 31.5 years at time of pre-CIS blood sampling; mean age at disease onset 33.4 years) were available, covering an interval of 7.3 years-2 months (mean 31.5 months) before CIS. In 18 of 25 patients serum samples were also obtained after established diagnosis of MS. Longitudinal age- and gender-matched healthy blood donors (four male subjects, 21 female subjects, 39 samples, mean age 32.5 years) served as controls. Serum 25-OH-D was measured by isotope dilution-liquid chromatography-tandem mass spectrometry. 25-OH-D levels were deconvoluted using published seasonal coefficients from a German population. Immunoglobulin G (IgG) against Epstein-Barr virus nuclear antigen-1 (EBNA1) were assessed using commercially available ELISA. Results Low 25-OH-D levels were observed during the 24-month pre-CIS interval (47.8 (32.5-77.2) nmol/l, median (IQR); healthy controls: 81.6 (57.7-98.5), p=0.004, however, still higher than after established diagnosis (24.5 (13.7-47.7), p<0.0001 compared with controls). IgG against EBNA1 during the 36-month pre-CIS interval was increased (185.9 (91.2-460.0) IU/ml, median (IQR); healthy controls 63.7 (29.5-121.6), p=0.002). Conclusions Low vitamin D and remote EBV infection may be associated with clinical MS breakthrough within 2-3 years."],["dc.identifier.doi","10.1136/jnnp-2012-303068"],["dc.identifier.isi","000311097700012"],["dc.identifier.pmid","22888143"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24794"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bmj Publishing Group"],["dc.relation.issn","0022-3050"],["dc.title","Low vitamin D and elevated immunoreactivity against Epsteine-Barr virus before first clinical manifestation of multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Clinical Chemistry"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Domke, I."],["dc.contributor.author","Shipkova, Maria"],["dc.contributor.author","Engelmayer, J."],["dc.contributor.author","Kheradmand, M."],["dc.contributor.author","Luthe, Hilmar"],["dc.contributor.author","Pou, L."],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Vukovich, T."],["dc.contributor.author","Oellerich, M."],["dc.contributor.author","Wieland, Eberhard"],["dc.date.accessioned","2018-11-07T09:44:11Z"],["dc.date.available","2018-11-07T09:44:11Z"],["dc.date.issued","2006"],["dc.format.extent","A61"],["dc.identifier.isi","000237925900188"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34335"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Clinical Chemistry"],["dc.publisher.place","Washington"],["dc.relation.conference","58th Annual Meeting of the American-Association-of-Clinical-Chemistry"],["dc.relation.eventlocation","Chicago, IL"],["dc.relation.issn","0009-9147"],["dc.title","Cyclosporin determination with different immunoassays in four laboratories using routine patient samples from different transplant types: Performance of automated immunoassays and comparability to tandem mass spectrometry"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","63"],["dc.bibliographiccitation.journal","Forensic Science International"],["dc.bibliographiccitation.lastpage","73"],["dc.bibliographiccitation.volume","287"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kaufmann, Christoph"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Binder, Lutz"],["dc.date.accessioned","2020-12-10T14:24:10Z"],["dc.date.available","2020-12-10T14:24:10Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.forsciint.2018.03.039"],["dc.identifier.issn","0379-0738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72169"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Systematic forensic toxicological analysis by liquid-chromatography-quadrupole-time-of-flight mass spectrometry in serum and comparison to gas chromatography-mass spectrometry"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","428"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","433"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Marquet, Pierre"],["dc.contributor.author","Liebisch, Gerhard"],["dc.contributor.author","Schmitz, Gerd"],["dc.contributor.author","Coffing, Mary Jane"],["dc.contributor.author","Domke, Ingrid"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Luthe, Hilmar"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Shaw, Leslie M."],["dc.date.accessioned","2021-06-01T10:46:58Z"],["dc.date.available","2021-06-01T10:46:58Z"],["dc.date.issued","2008"],["dc.description.abstract","The performance characteristics of a new inosine monophosphate dehydrogenase inhibition assay for the quantification of total mycophenolic acid (MPA) in plasma (Roche Diagnostics) were assessed in a multicenter evaluation. Validation data were collected from four institutions. Within-run and total imprecision were acceptable (n = 21 for each of 7 materials, coefficients of variation ranging 0.7-9.6%). The lower limit of quantification was 0.31 mg/L. The assay was linear from 0.31 to 15.0 mg/L. Method comparison with validated high-performance liquid chromatography with ultraviolet light or liquid chromatography tandem mass spectrometry methods showed good agreement (coefficients of correlation 0.974-0.994, slopes 1.01-1.17, intercepts -0.17 to 0.06). There was no difference found between results from different transplant types (cardiac vs. renal) or comedications (cyclosporine vs. tacrolimus). The recovery of samples from a proficiency testing scheme was acceptable. The cross-reactivity of AcMPAG, an in vitro active metabolite of MPA, was examined by adding AcMPAG to a pool of patient samples and subsequent quantification. MPA overestimation by AcMPAG cross-reactivity was found to be low (< 5%). Thus, this interference is expected to be clinically irrelevant. In conclusion, the Roche Total MPA assay is a promising alternative for MPA quantification where chromatographic methods are not available."],["dc.identifier.doi","10.1097/FTD.0b013e31817fd590"],["dc.identifier.isi","000258114900004"],["dc.identifier.pmid","18641549"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85437"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Multicenter Evaluation of a New Inosine Monophosphate Dehydrogenase Inhibition Assay for Quantification of Total Mycophenolic Acid in Plasma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","123"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","131"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Barten, Markus J."],["dc.contributor.author","Shipkova, Maria"],["dc.contributor.author","Bartsch, P."],["dc.contributor.author","Dhein, S."],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Tarnok, A."],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Mohr, F. W."],["dc.contributor.author","Oellerich, M."],["dc.contributor.author","Gummert, J. E."],["dc.date.accessioned","2018-11-07T11:14:21Z"],["dc.date.available","2018-11-07T11:14:21Z"],["dc.date.issued","2005"],["dc.description.abstract","The effect of mycophenolic acid (MPA) in combination with either cyclosporine (CsA) or tacrolimus (TRL) on whole-blood lymphocyte function was assessed in vitro as well as in vivo. For the in vitro studies, rat whole blood was incubated with different concentrations of MPA together with CsA or TRL. In vivo, rats (n = 6 per group) were orally treated with 2.5 or 5 ing/kg of mycophenolate mofetil (MMF), either alone or in combination with 5 mg/kg CsA or 4 mg/kg TRL. Blood was obtained before and at different times after dosing. For both in vitro and in vivo studies, mitogen-stimulated whole blood was analyzed by flow cytometry to determine inhibition of expression of lymphocyte proliferation (proliferating cell nuclear antigen, PCNA) and T-cell activation (eg, CD25). Plasma MPA concentrations were measured by HPLC, and whole-blood CsA and TRL concentrations were quantified using LC-MS/MS. In vitro, low concentrations of 250 and 500 nM MPA acted additively with CsA and overadditively with TRL to suppress lymphocyte function, whereas higher MPA concentrations (1000 nM) in these combinations did not further increase inhibition compared with monotherapy with CsA or TRL alone. In vivo, the MPA AUC(O-24) showed a dose-dependent increase. CsA and TRL AUC(O-24) were not influenced by the MMF dose. Combination therapy increased inhibition of lymphocyte function compared with MMF monotherapy with a pronounced effect on PCNA compared with CD25. Significant differences between 2.5 and 5 mg/kg MMF in the combination groups were observed at 2 or 6 hours after dosing because of the maximal inhibitory effect oil PCNA and CD25 expression (P < 0.05, ANOVA), However, in combination with TRL no different effects on the inhibition of CD25 expression were found between the 2 MMF doses. These novel data indicate that measurement of pharmacodynamic parameters of lymphocyte function in whole blood may help to monitor drug combination therapy and provide a rationale for drug reduction to minimize toxicity without compromising efficacy."],["dc.identifier.doi","10.1097/01.ftd.0000146874.11480.8a"],["dc.identifier.isi","000228115500003"],["dc.identifier.pmid","15795640"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54104"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Mycophenolic acid interaction with cyclosporine and tacrolimus in vitro and in vivo - Evaluation of additive effects on rat blood lymphocyte function"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","327"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Breastfeeding Medicine"],["dc.bibliographiccitation.lastpage","329"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Mueller, Matthias J."],["dc.contributor.author","Preuss, Christoph"],["dc.contributor.author","Paul, Thomas"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Seeliger, Stephan"],["dc.date.accessioned","2018-11-07T09:24:13Z"],["dc.date.available","2018-11-07T09:24:13Z"],["dc.date.issued","2013"],["dc.description.abstract","The selective serotonin reuptake inhibitor (SSRI) sertraline is widely used as an antidepressant agent during pregnancy and lactation because of its low placental transfer and low level of excretion into breastmilk. Symptoms such as neonatal abstinence syndrome and serotonergic overstimulation have been reported after in utero exposure to SSRIs. These symptoms are self-limiting and usually peak within the first 48 hours after birth. In our case, a preterm infant was exposed to sertraline and its main metabolite desmethylsertraline in utero and via breastmilk. Beyond the first 48 hours after birth, the infant developed increasing clinical signs of serotonergic overstimulation associated with substance intake via breastmilk, until breastfeeding was discontinued on postnatal Day 9. In spite of a low calculated daily substance intake via breastmilk, the serum substance levels of the preterm infant were within the therapeutic range of adults. The serotonergic overstimulation may be explained by the limited metabolic capacity of the infant and the immaturity of the blood-brain barrier."],["dc.identifier.doi","10.1089/bfm.2012.0084"],["dc.identifier.isi","000319458000014"],["dc.identifier.pmid","23249132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29771"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mary Ann Liebert Inc"],["dc.relation.issn","1556-8253"],["dc.title","Serotonergic Overstimulation in a Preterm Infant After Sertraline Intake via Breastmilk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1174"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.lastpage","1185"],["dc.bibliographiccitation.volume","44"],["dc.contributor.affiliation","Klemp, Henry; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Nessler, Stefan; 2\r\nInstitute of Neuropathology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Streit, Frank; 3\r\nInstitute for Clinical Chemistry, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Krätzner, Ralph; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Rosewich, Hendrik; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Gärtner, Jutta; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Klemp, Henry"],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Krätzner, Ralph"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-06-01T09:42:02Z"],["dc.date.available","2021-06-01T09:42:02Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T01:43:41Z"],["dc.description.abstract","Abstract X‐linked adrenoleukodystrophy (X‐ALD) is the most common leukodystrophy. Despite intensive research in recent years, it remains unclear, what drives the different clinical disease courses. Due to this missing pathophysiological link, therapy for the childhood cerebral disease course of X‐ALD (CCALD) remains symptomatic; the allogenic hematopoietic stem cell transplantation or hematopoietic stem‐cell gene therapy is an option for early disease stages. The inclusion of dried blood spot (DBS) C26:0‐lysophosphatidylcholine to newborn screening in an increasing number of countries is leading to an increasing number of X‐ALD patients diagnosed at risk for CCALD. Current follow‐up in asymptomatic boys with X‐ALD requires repetitive cerebral MRIs under sedation. A reliable and easily accessible biomarker that predicts CCALD would therefore be of great value. Here we report the application of targeted metabolomics by AbsoluteIDQ p180‐Kit from Biocrates to search for suitable biomarkers in X‐ALD. LysoPC a C20:3 and lysoPC a C20:4 were identified as metabolites that indicate neuroinflammation after induction of experimental autoimmune encephalitis in the serum of Abcd1tm1Kds mice. Analysis of serum from X‐ALD patients also revealed different concentrations of these lipids at different disease stages. Further studies in a larger cohort of X‐ALD patient sera are needed to prove the diagnostic value of these lipids for use as early biomarkers for neuroinflammation in CCALD patients."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Niedersächsisches Ministerium für Wissenschaft und Kultur http://dx.doi.org/10.13039/501100010570"],["dc.description.sponsorship","Germany's Excellence Strategy"],["dc.description.sponsorship","Transregional Collaborative Research Center"],["dc.identifier.doi","10.1002/jimd.12389"],["dc.identifier.pmid","33855724"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85119"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/270"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1573-2665"],["dc.relation.issn","0141-8955"],["dc.relation.workinggroup","RG Gärtner"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."],["dc.title","Targeted metabolomics revealed changes in phospholipids during the development of neuroinflammation in Abcd1 tm1Kds mice and X‐linked adrenoleukodystrophy patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Dogan, Ahmet"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2018-11-07T11:00:31Z"],["dc.date.available","2018-11-07T11:00:31Z"],["dc.date.issued","2007"],["dc.format.extent","518"],["dc.identifier.isi","000248359200201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50935"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","10th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology"],["dc.relation.eventlocation","Nice, FRANCE"],["dc.relation.issn","0163-4356"],["dc.title","Simultaneous determination of clozapine, olanzapine and quetiapine using the waters quattro micro((R)) system with a ESI interface"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S0960076021000431"],["dc.bibliographiccitation.firstpage","105850"],["dc.bibliographiccitation.journal","The Journal of Steroid Biochemistry and Molecular Biology"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Koepp, Regine"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Beismann, Johannes"],["dc.contributor.author","Manthey, Georg"],["dc.contributor.author","Seitz, Mark-Tilmann"],["dc.contributor.author","Kragl, Angelique"],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2021-07-05T15:00:19Z"],["dc.date.available","2021-07-05T15:00:19Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1016/j.jsbmb.2021.105850"],["dc.identifier.pii","S0960076021000431"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87797"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.issn","0960-0760"],["dc.title","The rise in expression and activity of 11β-HSD1 in human mesenchymal progenitor cells induces adipogenesis through increased local cortisol synthesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","632"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","643"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Hafke, Angelika"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Braulke, Friederike"],["dc.contributor.author","Haase, Detlef"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Walson, Philip D."],["dc.date.accessioned","2018-11-07T08:51:25Z"],["dc.date.available","2018-11-07T08:51:25Z"],["dc.date.issued","2011"],["dc.description.abstract","Objectives: Trough total imatinib (t-IM) concentrations have been reported to be associated with therapeutic and toxic responses in patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST). Little is known about the relationships between effects and concentrations of either unbound imatinib (f-IM) or imatinib's major metabolite, N-desmethyl imatinib (NDI). In part, this is because of the lack of a single, validated, well-described clinically useful assay for these measurements. The authors report the development and application of such an assay. Materials and Methods: A single liquid-chromatography tandem-mass-spectrometry assay was used to monitor t-IM, f-IM, and t-NDI concentrations in CML and GIST patients treated at a tertiary German teaching hospital. The assay was also validated for measuring other kinase inhibitors, including t-nilotinib, sunitinib, and erlotinib. Ultrafiltration assays were validated and used to measure f-IM and to compare free fractions to plasma alpha(1)-acid glycoprotein concentrations (AGP). Results: The assays were linear over a working range (in micrograms per liter) of 8.4-8370, 8.3-4165, and 1.0-250 and had within-and between-run coefficient of variance of <7%, <12%, and <9% for t-IM, t-NDI, and f-IM, respectively. The f-IM assay was reproducible despite high (25.2%-31.6%) but concentration-independent binding to ultrafiltration devices. Clinically relevant results, such as nondetectable (ND) t-IM (<8.4 mu g/L) in non-responders and >1500 mu g/L in patients with major toxicity, were found. Of 156 total samples from 68 adult CML patients and 127 total samples from 42 adult GIST, only 48 samples from 22 CML patients and 40 samples from 20 GIST patients were trough samples with adequate dosing and collection information. More than half (27 of 48 CML and 24 of 40 GIST) had t-IM concentrations >= 10% below recommended target concentrations (1002 mu g/L for CML and 1100 mu g/L for GIST). Concentrations.50% over targets were also found in 6 of 48 CML and 4 of 40 GIST samples. Wide variations in concentrations of t-IM (range, ND to 2973 mu g/L), t-NDI (range, ND to 659 mu g/L), f-IM (range, 8.3-262 mu g/L), and t-IM:f-IM ratios (range, 2.6%-14%) were found both between and within patients. A statistically significant association (Spearman correlation coefficient and P value for all samples, r = 0.290 and P = 0.023; for trough only, r = -0.585 and P = 0.028) was found between AGP and f-IM concentrations but wide interpatient and intrapatient variations made individual predictions unreliable. Conclusions: The liquid-chromatography tandem-mass-spectrometry methods developed provided information useful to understand individual responses to therapy even though necessary sampling and dosing information was often not available. Wide unpredictable variations in t-IM, t-NDI, and f-IM were found. Clinical outcome trials are needed to examine whether f-IM or NDI monitoring can improve the ability to predict individual responses."],["dc.description.sponsorship","Novartis Pharma GmbH, Nuernberg, Germany"],["dc.identifier.doi","10.1097/FTD.0b013e3182263ac4"],["dc.identifier.isi","000295083000009"],["dc.identifier.pmid","21912334"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21930"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Use of Total and Unbound Imatinib and Metabolite LC-MS/MS Assay to Understand Individual Responses in CML and GIST Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]