Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Witt, Lukas [VerfasserIn]   i
 Hohmann, Nicolas [VerfasserIn]   i
 Mikus, Gerd [VerfasserIn]   i
 Haefeli, Walter E. [VerfasserIn]   i
 Burhenne, Jürgen [VerfasserIn]   i
Titel:Ultrasensitive quantification of the CYP2E1 probe chlorzoxazone and its main metabolite 6-hydroxychlorzoxazone in human plasma using ultra performance liquid chromatography coupled to tandem mass spectrometry after chlorzoxazone microdosing
Verf.angabe:Lukas Witt, Yosuke Suzuki, Nicolas Hohmann, Gerd Mikus, Walter E. Haefeli, Jürgen Burhenne
Umfang:7 S.
Fussnoten:Gesehen am 05.01.2017
Titel Quelle:Enthalten in: Journal of chromatography / B
Jahr Quelle:2016
Band/Heft Quelle:1027(2016), S. 207-213
ISSN Quelle:1873-376X
Abstract:Chlorzoxazone is a probe drug to assess cytochrome P450 (CYP) 2E1 activity (phenotyping). If the pharmacokinetics of the probe drug is linear, pharmacologically ineffective doses are sufficient for the purpose of phenotyping and adverse effects can thus be avoided. For this reason, we developed and validated an assay for the ultrasensitive quantification of chlorzoxazone and 6-hydroxychlorzoxazone in human plasma. Plasma (0.5 mL) and liquid/liquid partitioning were used for sample preparation. Extraction recoveries ranged between 76 and 93% for both analytes. Extracts were separated within 3 min on a Waters BEH C18 Shield 1.7 μm UPLC column with a fast gradient consisting of aqueous formic acid and acetonitrile. Quantification was achieved using internal standards labeled with deuterium or 13C and tandem mass spectrometry in the multiple reaction monitoring mode using negative electrospray ionization, which yielded lower limits of quantification of 2.5 pg mL−1, while maintaining a precision always below 15%. The calibrated concentration ranges were linear for both analytes (2.5-1000 pg mL−1) with correlation coefficients of >0.99. Within-batch and batch-to-batch precision in the calibrated ranges for both analytes were <15% and <11% and plasma matrix effects always were below 50%. The assay was successfully applied to assess the pharmacokinetics of chlorzoxazone in two human volunteers after administration of single oral doses (2.5-5000 μg). This ultrasensitive assay allowed the determination of chlorzoxazone pharmacokinetics for 8 h after microdosing of 25 μg chlorzoxazone.
DOI:doi:10.1016/j.jchromb.2016.05.049
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Verlag: http://www.sciencedirect.com/science/article/pii/S1570023216303622
 Verlag: http://dx.doi.org/10.1016/j.jchromb.2016.05.049
 Verlag: http://www.sciencedirect.com/science/article/pii/S1570023216303622
 DOI: https://doi.org/10.1016/j.jchromb.2016.05.049
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1551468999
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68069513   QR-Code
zum Seitenanfang