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

摘要

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 C-18 column (150 mm x 3.0 mm, 3.0 mu m). 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 20 mg/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. (C) 2015 Elsevier B.V. All rights reserved.