title: 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.
abstract: 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.
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors: Dominika
authors: D
authors: Bratkowska
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors: Adeola
authors: A
authors: Shobo
authors: Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors: Sanil
authors: S
authors: Singh
authors: Biomedical Resource Unit, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors: Linda
authors: L
authors: A Bester
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors: Hendrik G
authors: HG
authors: Kruger
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors: Glenn E M
authors: GE
authors: Maguire
authors: Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa. Electronic address: govenderthav@ukzn.ac.za.
authors: Thavendran
authors: T
authors: Govender
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D016014:Linear Models; D008168:Lung / Q000737:chemistry; D009593:Nitroimidazoles / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000995:Antitubercular Agents; D009593:Nitroimidazoles; C410767:pretomanid
keywords: LC–(ESI)MS/MS; PA-824; Pharmacokinetics; Rat plasma; Rat tissues; Tuberculosis