Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS).
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Bai F, Tagen M, Colotta C, Miller L, Fouladi M, Stewart CF
Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS).
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2348-52. doi: 10.1016/j.jchromb.2010.07.019. Epub 2010 Jul 30.
- PubMed ID
- 20702149 [ View in PubMed]
- Abstract
A sensitive and rapid HTLC-ESI-MS/MS method with an advanced online sample preparation was developed for determination of the gamma-secretase inhibitor MK-0752 in human plasma using an internal standard. Plasma samples (100 microL) were diluted and injected directly onto an online extraction column (Cohesive Cyclone MAX 0.5 mm x 50 mm, > 30 microm), the sample matrix was washed out with an aqueous solution, and retained analytes were eluted out and transferred directly to the analytical column (Phenomenex Gemini 3 micron C18 110A, 50 mm x 2.0 mm at 50 degrees C) for separation using a gradient mobile phase. The eluted analytes were then detected on an API-3000 LC-MS/MS System with ESI and a negative multiple reaction monitoring mode. The monitored ion transitions were m/z 441-->175 for MK-0752 and 496-->175 for the internal standard. Online extraction recoveries were 81%. The method was validated and was linear in the range of 0.05-50 microg/mL. Within-day and between-day precisions were<8.6%, and accuracies were 0.7 and 7.1%. This method was applied to the measurement of plasma MK-0752 levels in a Phase I study of pediatric patients with recurrent or refractory brain tumors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions MK-0752 Gamma-secretase subunit APH-1A Protein Humans UnknownInhibitorDetails