Liquid chromatography-tandem mass spectrometric assay for the determination of tetrabenazine and its active metabolites in human plasma: a pharmacokinetic study.

Autor: Derangula VR; Research Studies, Rayalaseema University, Kurnool-, 518 002, India., Pilli NR, Nadavala SK, Adireddy V, Inamadugu JK, Ponneri V
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2013 Jun; Vol. 27 (6), pp. 792-801. Date of Electronic Publication: 2013 Jan 21.
DOI: 10.1002/bmc.2862
Abstrakt: A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for the simultaneous quantification of tetrabenazine and its active metabolites α-dihydrotetrabenazine and β-dihydrotetrabenazine in human plasma. Tetrabenazine d7 was used as internal standard (IS). The analytes were extracted from 200 μL aliquots of human plasma via solid-phase extraction using C18 solid-phase extraction cartridges. The reconstituted samples were chromatographed on a Zorbax SB C18 column using a 60:40 (v/v) mixture of acetonitrile and 5 mm ammonium acetate as the mobile phase at a flow rate of 0.8 mL/min. The API-4000 LC-MS/MS in multiple reaction-monitoring mode was used for detection. The calibration curves obtained were linear (r(2) ≥ 0.99) over the concentration range of 0.01-5.03 ng/mL for tetrabenazine and 0.50-100 ng/mL for α-dihydrotetrabenazine and β-dihydrotetrabenazine. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The method is precise and sensitive enough for its intended purpose. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.
(Copyright © 2013 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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