Next Article in Journal
The Challenge of Ecophysiological Biodiversity for Biotechnological Applications of Marine Microalgae
Previous Article in Journal
Chemistry and Biology of Bengamides and Bengazoles, Bioactive Natural Products from Jaspis Sponges
Open AccessArticle

Largazole Pharmacokinetics in Rats by LC-MS/MS

1
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
2
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
3
Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA
4
Department of Chemistry, Duke University, Durham, NC 27708, USA
5
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
6
Marine Science Institute, College of Science, University of the Philippines, Diliman, Quezon City, 1100, Philippines
*
Author to whom correspondence should be addressed.
Mar. Drugs 2014, 12(3), 1623-1640; https://doi.org/10.3390/md12031623
Received: 14 October 2013 / Revised: 30 January 2014 / Accepted: 27 February 2014 / Published: 20 March 2014
A highly sensitive and specific LC-MS/MS method for the quantitation of largazole thiol, the active species of the marine-derived preclinical histone deacetylase inhibitor, largazole (prodrug), was developed and validated. Largazole thiol was extracted with ethyl acetate from human or rat plasma along with the internal standard, harmine. Samples were separated on an Onyx Monolithic C18 column by a stepwise gradient elution with 0.1% formic acid in methanol and 0.1% aqueous formic acid employing multiple reaction monitoring (MRM) detection. Linear calibration curves were obtained in the range of 12.5–400 ng/mL with 200 µL of human plasma. The overall intra-day precision was from 3.87% to 12.6%, and the inter-day precision was from 7.12% to 9.8%. The accuracy at low, medium and high concentrations ranged from 101.55% to 105.84%. Plasma protein bindings of largazole thiol in human and rat plasma as determined by an ultrafiltration method were 90.13% and 77.14%, respectively. Plasma drug concentrations were measured by this LC-MS/MS method. The pharmacokinetics of largazole thiol in rats was studied following i.v. administration at 10 mg/kg and found to follow a two-compartment model. Largazole thiol was rapidly eliminated from systemic circulation within 2 h. The established LC-MS/MS method is suitable for the analysis of largazole thiol in human plasma, as well. View Full-Text
Keywords: largazole; LC-MS/MS; pharmacokinetics; protein binding largazole; LC-MS/MS; pharmacokinetics; protein binding
Show Figures

Graphical abstract

MDPI and ACS Style

Yu, M.; Salvador, L.A.; Sy, S.K.B.; Tang, Y.; Singh, R.S.P.; Chen, Q.-Y.; Liu, Y.; Hong, J.; Derendorf, H.; Luesch, H. Largazole Pharmacokinetics in Rats by LC-MS/MS. Mar. Drugs 2014, 12, 1623-1640.

Show more citation formats Show less citations formats

Article Access Map

1
Only visits after 24 November 2015 are recorded.
Back to TopTop