期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 209, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jpba.2021.114525
关键词
Assay; Tandem mass spectrometry; Terameprocol; Validation
资金
- Adult Brain Tumor Consortium (National Institutes of Health (NIH)) [UM1CA137443]
- Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [NIH] [P30CA006973, UL1TR003098, S10OD020091, S10 RR026824]
- Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [S10OD020091, S10 RR026824]
- National Center for Advancing Translational Sciences (NCATS) , a component of the NIH Roadmap for Medical Research [UL1TR003098]
A sensitive and reliable method for quantitating terameprocol was developed using LC-MS/MS, enabling detailed pharmacokinetic studies for the treatment of high-grade glioma. The method demonstrated accurate and precise measurements, with stability of terameprocol in plasma for at least 20 months when stored at -70 degrees C.
The global transcription inhibitor terameprocol is being evaluated clinically as an oral formulation to treat high-grade glioma. A sensitive, reliable method was developed to quantitate terameprocol using LC-MS/MS to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of terameprocol and the internal standard, Sorafenib-methyl-d3, was achieved with a Zorbax XDB C18 column (2.1 x 50 mm, 3.5 mu m) and gradient elution over a 2-minute total analytical run time. A SCIEX 4500 or SCIEX 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for terameprocol detection. The assay range of 5-1000 ng/mL was demonstrated to be accurate (92.7-107.4%) and precise (CV <= 11.3%). A sample diluted 1:10 (v/v) was accurately quantitated. Terameprocol in plasma has been proven stable for at least 20 months when stored at -70 degrees C. The method was applied to the measurement of total plasma concentrations of terameprocol in a patient with a high-grade glioma receiving a 300 mg oral dose. (c) 2021 Elsevier B.V. All rights reserved.
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