Determination of the antitubercular drug PA-824 in rat plasma, lung and brain tissues by liquid chromatography tandem mass spectrometry: application to a pharmacokinetic study.

Authors:
Dominika Bratkowska
Dominika Bratkowska
Universitat Rovira i Virgili
Spain
Dr Adeola Shobo, PhD
Dr Adeola Shobo, PhD
McGill University
Dr
Montreal , McGill University | Canada
Sanil Singh
Sanil Singh
University of KwaZulu-Natal
South Africa
Linda A Bester
Linda A Bester
University of KwaZulu-Natal
Pietermaritzburg | South Africa
Hendrik G Kruger
Hendrik G Kruger
University of KwaZulu-Natal
South Africa

J Chromatogr B Analyt Technol Biomed Life Sci 2015 Apr 9;988:187-94. Epub 2015 Mar 9.

Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa. Electronic address:

A selective, sensitive and high performance liquid chromatography-tandem mass spectrometry (LC-(ESI)MS/MS) method has been developed and validated for the quantification of the potent antitubercular drug candidate, PA-824, in rat plasma, lung and brain tissues. Sample clean-up involved protein precipitation and solid-phase extraction. Chromatographic separation was performed on YMC Triart C18 column (150 mm × 3.0 mm, 3.0 μm). The method was validated over the concentration range of 75-1500 ng/mL for plasma, 50-1200 ng/g for lungs and 100-1500 ng/g for brain tissue. Evaluation of the pharmacokinetic properties of PA-824 utilized Sprague Dawley rats with a dosage of 20mg/kg at various time points. The new method was applied successfully for the determination of PA-824 with liquid desorption followed by liquid chromatography with ultra-high resolution quadrupole time-of-flight mass spectrometry in the different biological samples.

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http://dx.doi.org/10.1016/j.jchromb.2015.02.041DOI Listing
April 2015
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